Born in Melbourne, Australia, Caldicott attended the Fintona Girls' School, and received her medical degree in 1961 from the University of Adelaide Medical School. In 1977 she joined the staff of the Children's Hospital Medical Center in Boston, and taught pediatrics at the Harvard Medical School from 1977 to 1978.

In 1980, following the Three Mile Island nuclear accident, she left her medical career in order to concentrate on calling the world's attention to what she refers to as the "insanity" of the nuclear arms race and the growing reliance on nuclear power.

In 1982, she was the subject of the controversial Oscar-winning National Film Board of Canada documentary on the dangers of nuclear weapons, entitled If You Love This Planet.

Citing confidential memos, Caldicott says that the Hershey Foods Corporation was concerned about radiation levels in milk used in their products because of the proximity of the Three Mile Island accident to Hershey's Pennsylvania factory. According to Caldicott, citing a March 30, 1979 study by the Pennsylvania State University, College of Engineering, radiation contaminants that fell on the Pennsylvania grass found its way into the milk of the local dairy cows. Caldicott noted this was contrary to the findings in the government official report released shortly after the Three Mile Island disaster. Caldicott disputes this report in her book, Nuclear Power is Not the Answer.

Also in 1980, she founded the Women's Action for Nuclear Disarmament (WAND) in the United States, which was later renamed Women's Action for New Directions. It is a group dedicated to reducing or redirecting government spending away from nuclear energy use towards what the group perceives as unmet social issues.

During her time in the United States from 1977 to 1986, Caldicott was involved with Physicians for Social Responsibility (founded originally in 1961), an organization of 23,000 doctors committed to educating others on what they claimed were the dangers of nuclear energy. She also worked abroad to establish similar groups that focused on education about what she said were risks of nuclear energy, nuclear weapons and nuclear war. One such international group (International Physicians for the Prevention of Nuclear War) was awarded the Nobel Peace Prize in 1985. She herself received the Humanist of the Year award from the American Humanist Association in 1982.

Caldicott's investigative writings had the distinction of being nominated and subsequently chosen as Project Censored's #2 story in 1990. Citing the research of Soviet scientists Valery Burdakov and Vyacheslav Fiin, Caldicott argued that NASA's Space Shuttle program was destroying the Earth’s ozone and that 300 total shuttle flights would be enough to "completely destroy the Earth's protective ozone shield," although there is no scientific evidence to back up this claim.

In 1995 Caldicott returned to the US where she lectured for the New School of Social Research on the Media, Global Politics, and the Environment. She also hosted a weekly radio show on WBAI (Pacifica) and became the Founding President of the STAR (Standing for Truth About Radiation) Foundation.

Her sixth book, The New Nuclear Danger: George W. Bush’s Military Industrial Complex, was published in 2001. While touring with that book, she founded the Nuclear Policy Research Institute, headquartered in Washington, DC. NPRI seeks to facilitate an ongoing public education campaign in the mainstream media about what it perceives as the dangers of nuclear energy, including weapons and power programs and policies. It is led by both Caldicott and Executive Director Julie R. Enszer. NPRI has attempted to create a consensus to end all uses of nuclear energy and destroy the nuclear age by means of public education campaigns, establishing a presence in the mainstream media, and sponsoring high-profile symposia.

In May 2003, Caldicott gave a lecture entitled "The New Nuclear Threat" at the University of San Diego's Joan B. Kroc Institute for Peace & Justice Distinguished Lecture Series.

A 2004 documentary film, 'Helen's War: portrait of a dissident', provides a look into Dr. Caldicott's life through the eyes of her niece, filmmaker Anna Broinowski.

Caldicott currently splits her time between the United States and Australia and continues to lecture widely to promote her views on nuclear energy use, including weapons and power. She has been awarded 20 honorary doctoral degrees and was nominated for the Nobel Peace Prize by Nobel Laureate Linus Pauling. She was awarded the Lannan Foundation Prize for Cultural Freedom in 2003, and in 2006, the Peace Organisation of Australia presented her with the inaugural Australian Peace Prize "for her longstanding commitment to raising awareness about the medical and environmental hazards of the nuclear age". The Smithsonian Institution has named Caldicott as one of the most influential women of the 20th century.

Since July 14, 2008, Dr. Caldicott has hosted an hour-long, weekly radio program, "If You Love This Planet." The show was first aired and originated by Houston station KPFT and is now heard on dozens of U.S., Australian and Canadian stations, and on its own website www.ifyoulovethisplanet.org.

A fully revised and updated edition of her 1992 book "If You Love This Planet" was published by W.W. Norton in September 2009.

Helen Caldicott is featured along with foreign affairs experts, space security activists and military officials in interviews in Denis Delestrac's 2010 feature documentary "Pax Americana and the Weaponization of Space".

Federal politics

Caldicott contested the New South Wales seat of Division of Richmond in the House of Representatives at the 1990 federal election, a seat held by conservatives since the inaugural 1901 election, and by the Country Party (now National Party) since it first contested elections at the 1922 election. Caldicott polled very well for a federal independent candidate, receiving 23.3 percent of the primary vote. On the sixth count, Caldicott had 27.4 percent of the vote, with Nationals incumbent (and then leader of the Nationals) Charles Blunt at 43.2 percent and Labor candidate Neville Newell at 29.4 percent. Calidcott was eliminated, and her preferences flowed heavily to Newell. This enabled Labor to take the seat for the first time in its history, on 50.5 percent of the two party preferred vote, a swing of 7.1 percent. This saw only one of three times a major party leader was defeated in his own seat at an election, the others being Stanley Bruce at the 1929 election and John Howard at the 2007 election.

Caldicott wished to enter the Australian Senate in 1991 and attempted to win Australian Democrats' support to replace New South Wales Senator Paul McLean, who had recently resigned. However, the party chose the highest unelected person on their New South Wales Senate ticket from the previous election and Karin Sowada took the position.