Ledeen holds a Ph.D. from the University of Wisconsin—Madison, where he specialized in Modern Europe. At Washington University in St. Louis, Ledeen was denied tenure, according to history department faculty interviewed by the Washington Post, because of questions regarding the "quality of his scholarship" and about whether Ledeen had "used the work of somebody else without proper credit". One faculty member said "the 'quasi-irregularity' at issue didn't warrant the negative vote on tenure for Ledeen".

Ledeen was subsequently named Visiting Professor at the University of Rome. One of Ledeen's principal mentors was the Jewish German-born historian George Mosse, for whom he was research assistant at the time. Mosse wrote two famous books on National Socialism. Another major influence on Ledeen was the Italian historian Renzo De Felice. Ledeen held political views which stress "the urgency of combating centralized state power and the centrality of human freedom" that are said to have influenced or inspired the Bush administration.

Earlier in his career, Ledeen authored Universal Fascism: The Theory and Practice of the Fascist International, 1928-1936, published in 1972 and now out of print. The book, which was his doctoral dissertation, was the first work to explore Italian leader Benito Mussolini's efforts to create a Fascist international in the late 1920s and early 1930s. Ledeen follows Italian historian Renzo de Felice in drawing a distinction between "fascism-regime" and "fascism-movement", and seems to approve of at least one aspect of the latter, saying "fascism nevertheless constituted a political revolution in Italy. For the first time, there was an attempt to mobilize the masses and to involve them in the political life of the country", and describing the fascist state as "a generator of energy and creativity". Ledeen continued his studies in Italian Fascism with a study of the takeover of Fiume by Italian irredentist forces under Gabriele d'Annunzio, who Ledeen argued was the proto-type for Mussolini.

Ledeen is a strong admirer of Niccolò Machiavelli, whom he regards as one of the greatest political thinkers. In Ledeen's view, Machiavelli combined democratic idealism and the necessary political realism to secure and defend idealism in perfect measure.

In 1980, in the period leading up to the U.S. presidential elections, Ledeen, along with Arnaud de Borchgrave, wrote a series of articles published in The New Republic and elsewhere about Billy Carter's contacts with the Muammar al-Gaddafi regime in Libya.

Ledeen has been accused of associations with shady organizations. For example, Jim Lobe has stated that "Ledeen's right-wing Italian connections — including alleged ties to the P2 masonic lodge that rocked Italy in the early 1980s — have long been a source of speculation and intrigue, but he returned to Washington in 1981 as 'anti-terrorism' advisor to the new secretary of state, Al Haig." While he acknowledges being paid by the SISMI in 1980 for "risk assessment", Ledeen denies any connections with Licio Gelli's masonic lodge. Ledeen told Vanity Fair that he had been paid $10,000 by the SISMI in 1979 or 1980 for advising them on extradition matters between Italy and the US. He denied having worked with [Francesco] Pazienza or Propaganda Due as part of a disinformation scheme. "I knew Pazienza," he explained. "I didn't think P-2 existed. I thought it was all nonsense — typical Italian fantasy." Pazienza, while at SISMI, did help Ledeen obtaining a tape confirming information on "Billygate."

It was during this time in Italy that Ledeen supported the "Bulgarian connection" conspiracy theory concerning Grey Wolves member Mehmet Ali A?ca's 1981 attempt to assassinate Pope John Paul II. The theory has since been attacked by various authors and journalists, including Washington Post reporter Michael Dobbs, who initially believed the story. The theory was adopted in 2005 by the Italian Mitrokhin Commission. A competing theory points toward Gladio, a NATO network believed to have supported the Turkish ultra-nationalist Grey Wolves and the strategy of tension in Italy, which had allegedly been supported by Gladio and SISMI agents. Gladio stay-behind networks directly responded to SACEUR. According to Craig Unger, "With Ronald Reagan newly installed in the White House, the so-called Bulgarian Connection made perfect Cold War propaganda. Michael Ledeen was one of its most vocal proponents, promoting it on TV and in newspapers all over the world."

In the early 1980s, Ledeen appeared before the newly established Senate Subcommittee on Security and Terrorism, alongside former CIA director William Colby, author Claire Sterling and former Newsweek editor Arnaud de Borchgrave. Both Ledeen and de Borchgrave worked for the Center for Strategic and International Studies at Georgetown University at the time. All four testified that they believed the Soviet Union had provided for material support, training and inspiration for various terrorist groupings.

Ledeen was a strong proponent of the theories in the book The Terror Network written by Claire Sterling that held that the USSR was the source of much of the international terrorism in the world.

Ledeen was involved in the Reagan administration's Iran-Contra scandal. As a consultant of National Security Advisor Robert C. McFarlane, Ledeen vouched for Iranian intermediary Manucher Ghorbanifar. In addition, he met with Israeli Prime Minister Shimon Peres, officials of the Israeli Foreign Ministry and the Central Intelligence Agency (CIA) to arrange meetings with high-ranking Iranian officials as well as the much-criticized weapons-for-hostages deal with Iran. Ledeen's own version of the events is published in his book, Perilous Statecraft.

Michael Ledeen had been accused of being involved in the forgery which claimed that Saddam Hussein had bought yellowcake in Niger.

According to Joshua Micah Marshall, Laura Rozen, and Paul Glastris noted in Washington Monthly of September 2004:

"The first meeting occurred in Rome in December, 2001. It included Franklin, Rhode, and another American, the neoconservative writer and operative Michael Ledeen, who organized the meeting. (According to UPI, Ledeen was then working for Undersecretary of Defense Douglas Feith as a consultant.) Also in attendance was Ghorbanifar and a number of other Iranians.

In 2005, Vincent Cannistraro, former head of counterterrorism operations at the CIA and the intelligence director at the National Security Council under Ronald Reagan, when asked by Ian Masters if Ledeen was the source of the forged memo, replied, "You'd be very close." However, just moments earlier when asked, "Do we know who produced those documents?" Cannistraro stated, " I’d rather not speak about it right now, because I don’t think it’s a proven case"

Former CIA counter-terrorism officer Philip Giraldi, who is Cannistraro's business partner and a columnist for The American Conservative, a paleoconservative magazine,said in an interview on July 26, 2005 that the forgeries were produced by "a couple of former CIA officers who are familiar with that part of the world who are associated with a certain well-known neoconservative who has close connections with Italy" and went on to confirm that he was referring to Ledeen. Giraldi added that the ex-CIA officers "also had some equity interests, shall we say, with the operation. A lot of these people are in consulting positions, and they get various, shall we say, emoluments in overseas accounts, and that kind of thing."

Giraldi more recently stated in The American Conservative:

At this point, any American connection to the actual forgeries remains unsubstantiated, though the OSP at a minimum connived to circumvent established procedures to present the information directly to receptive policy makers in the White House. But if the OSP is more deeply involved, Michael Ledeen, who denies any connection with the Niger documents, would have been a logical intermediary in co-ordinating the falsification of the documents and their surfacing, as he was both a Pentagon contractor and was frequently in Italy. He could have easily been assisted by ex-CIA friends from Iran-Contra days, including a former Chief of Station from Rome, who, like Ledeen, was also a consultant for the Pentagon and the Iraqi National Congress. It would have been extremely convenient for the administration, struggling to explain why Iraq was a threat, to be able to produce information from an unimpeachable “foreign intelligence source” to confirm the Iraqi worst-case. The possible forgery of the information by Defense Department employees would explain the viciousness of the attack on Valerie Plame and her husband. Wilson, when he denounced the forgeries in the New York Times in July 2003, turned an issue in which there was little public interest into something much bigger. The investigation continues, but the campaign against this lone detractor suggests that the administration was concerned about something far weightier than his critical op-ed.

Andrew McCarthy and Mark R. Levin have defended Ledeen, writing

Up until now, the fiction recklessly spewed by disgruntled intelligence-community retirees and their media enablers — some of whom have conceded that the claim is based on zero evidence — has been that Michael had something to do with the forged Italian documents that, according to the Left’s narrative, were the basis for President Bush’s “lie” in the 2003 State of the Union Address that Saddam Hussein had obtained yellowcake uranium (for nuclear-weapons construction) in Africa.

Regarding regime change in Iraq, in 2002 Ledeen criticized the views of former National Security Adviser Brent Scowcroft, writing:

He fears that if we attack Iraq "I think we could have an explosion in the Middle East. It could turn the whole region into a cauldron and destroy the War on Terror."

One can only hope that we turn the region into a cauldron, and faster, please. If ever there were a region that richly deserved being cauldronized, it is the Middle East today. If we wage the war effectively, we will bring down the terror regimes in Iraq, Iran, and Syria, and either bring down the Saudi monarchy or force it to abandon its global assembly line to indoctrinate young terrorists.

That's our mission in the war against terror.

Ledeen specifically called for the deposition of Saddam Hussein's regime by force in 2002:

So it's good news when Scowcroft comes out against the desperately-needed and long overdue war against Saddam Hussein and the rest of the terror masters.

and:

Question #2: Okay, well if we are all so certain about the dire need to invade Iraq, then when do we do so?

Ledeen: Yesterday

Ledeen's statements prior to the start of the Iraq war such as "desperately-needed and long overdue war against Saddam Hussein" and "dire need to invade Iraq" make his later statement that he "opposed the military invasion of Iraq before it took place" to be an "outright lie" to Glenn Greenwald. However, Ledeen maintains these statements are consistent since: "I advocated — as I still do — support for political revolution in Iran as the logical and necessary first step in the war against the terror masters."

Although Ledeen was in favor of assisting anti-Saddam forces in Iraq short of an invasion, he also believes that Iran should have been the first priority in the war on terror. The New York Times describes Ledeen's views as "everything traces back to Tehran". Ledeen's phrase, "faster, please" has become a signature meme in Ledeen's writings and is often referenced by neoconservative writers advocating a more forceful and broader war on terror. In 1979, Ledeen was one of the first Western writers to argue that Ayatollah Ruhollah Khomeini was a "clerical fascist", and that while it was legitimate to criticize the Shah's regime, if Khomeini seized power in Iran the Iranian people would suffer an even greater loss of freedom and women would be deprived of political and social rights. He presently believes that "No one in the West has yet supported Iranian democratic organizations" and that "aggressive support for those Iranians who wish to be free" would most likely work in ending the clerical government.

Ledeen is currently against both an invasion of Iran or air-strikes within the country. He has argued that the latter may eventually become necessary if negotiations with the Iranian government fail, but it would only be the least bad option of many options and it would lead to many negative unforeseen consequences. The New York Times has called Ledeen's skepticism towards military action against Iran surprising given his opposition to the regime. In October 2007, Ledeen argued that:

"Those who believe that I am part of some “hawkish gang” just haven’t noticed that I am opposed to invasion or bombing the nuclear facilities. My fear is that, by failing to promote a non-violent democratization of Iran, we make large-scale violence much more likely."

"In any event, time will tell, and I share the fear of most commenters [sic] that we will indeed arrive at a horrible choice between Iran with the bomb, or bomb Iran, as Sarkozy and Kouchner have put it. And if that happens, it will demonstrate a terrible failure on the part of the West, including the United States, to craft a serious Iran policy lo these many years."

Ledeen also believed that Iran is the main backer of the insurgency in Iraq and even supported the al-Qaida network formerly led by al-Zarqawi despite its declaration of jihad against Shi'ite Muslims. He claimed that German and Italian court documents showed Zarqawi created a European terrorist network while based in Tehran.

Ledeen was a board member of the "Coalition for Democracy in Iran" (CDI), founded by Morris Amitay, a former Executive Director of American Israel Public Affairs Committee (AIPAC). Ledeen had also been part of the board of the U.S. Committee for a Free Lebanon. According to the Washington Post, quoted by Asia Times, he was the only full-time international affairs analyst regularly consulted by Karl Rove, George W. Bush's closest advisor

In a 2003 column entitled "A Theory," Ledeen outlined a possibility that France and Germany, both NATO allies of the United States, "struck a deal with radical Islam and with radical Arabs" to use "extremism and terrorism as the weapon of choice" to bring down a potential American Empire. He stated, "It sounds fanciful, to be sure," but that, "If this is correct, we will have to pursue the war against terror far beyond the boundaries of the Middle East, into the heart of Western Europe. And there, as in the Middle East, our greatest weapons are political: the demonstrated desire for freedom of the peoples of the countries that oppose us." See also: Eurabia

Jonah Goldberg, Ledeen's colleague at National Review, coined the term "Ledeen Doctrine" in a 2002 column. This tongue-in-cheek "doctrine" is usually summarized as "Every ten years or so, the United States needs to pick up some small crappy little country and throw it against the wall, just to show the world we mean business," which Goldberg remembered Ledeen saying in an early 1990s speech.

Blogger Glenn Greenwald has taken Ledeen to task for his history of false statements and inaccurate predictions, calling him "one of the most dishonest and ludicrous jokes on the political scene."

Writing in The Nation, Jack Huberman, who describes Ledeen as "the most influential and unabashed warmonger of our time", attributes these quotes to Ledeen:

• "the level of casualties (in Iraq) is secondary"
• "we are a warlike people (Americans)...we love war"
• "Change — above all violent change — is the essence of human history"
• "the only way to achieve peace is through total war"
• "The purpose of total war is to permanently force your will onto another people"
• "Every ten years or so, the United States needs to pick up some small crappy little country and throw it against the wall, just to show the world we mean business"

The Buchananite journal, The American Conservative has claimed that Ledeen had strong sympathies for Italian fascism and that "Ledeen’s careful distinction between fascist 'regime' and 'movement' makes him a clear apologist for the latter." Ledeen is also scrutinized with some regularity at Antiwar.com, particularly by Justin Raimondo.

According to Christopher de Bellaigue of the New York Review of Books, Ledeen has purveyed a "distorted analysis of events in Iran" to his readers, claiming, for example, in National Review online that there were `something like a half a million` Iranians demonstrating the death sentence of Hashem Aghajari on November 22, 2002 when in fact Bellaigue, in Iran on that date, observed only about 5000 students in the biggest demonstration.

Ledeen is married to his second wife, Barbara. His first wife was Jenny Ledeen of St. Louis, Mo. Ledeen has three children: Simone, Gabriel, and Daniel. Simone has worked both in Iraq and Afghanistan for the Department of Defense; Gabriel is currently a Lieutenant in the United States Marines Corps serving his second tour in Iraq; and Daniel is currently serving a Lieutenant in the USMC.