Rosenbaum was born into a Jewish family in New York City, New York and grew up in Bay Shore, New York. He graduated from Yale University in 1968 and won a Carnegie Fellowship to attend Yale's graduate program in English Literature, though he dropped out after taking one course. He wrote for The Village Voice for several years, leaving in 1975 after which he wrote for Esquire, Harper's, High Times, Vanity Fair, New York Times Magazine and Slate.

Rosenbaum spent more than ten years doing research on Adolf Hitler including travels to Vienna, Munich, London, Paris, London, and Jerusalem, interviewing leading historians, philosophers, biographers, theologians and psychologists. Some of those interviewed by Rosenbaum included Daniel Goldhagen, David Irving, Rudolph Binion, Claude Lanzmann, Hugh Trevor-Roper, Alan Bullock, Christopher Browning, George Steiner, and Yehuda Bauer. The result was his 1998 book, The Search for the Origins of His Evil (Harper Collins. ISBN 0-679-43151-9).

In Explaining Hitler, Ron Rosenbaum also recounted in detail the previously little-reported story of the efforts of anti-Hitler journalists at the Munich Post who from 1920 to 1933, published repeated exposés on the criminal activities of the National Socialist German Workers Party (i.e. the Nazis). Matthew Ricketson, coordinator of the Journalism program at RMIT University's School of Applied Communication in Melbourne, Australia, called this book "a brilliant piece of research".

In 1987 he began writing a weekly column for the New York Observer called "The Edgy Enthusiast". He currently writes a column for Slate called The Spectator.

His most recent book is The Shakespeare Wars, which discussed recent controversies among literary historians, actors, and directors over how the works of William Shakespeare should be read, understood, and produced.

On Monday, June 28, 2010 he produced a controversial article in Slate called An Agnostic Manifesto. The article promoted a New Agnosticism to counter the rise in popularity of the New Atheism.

The article was widely criticised in the comments section of the same article. A strong source of criticism was his confusion of gnosticism and agnosticism (knowledge) with theism and atheism (religious faith) implying these terms are mutually exclusive when they are not. There was also criticism of his Straw Man portrayal of atheists.

Criticism also came from Matt Dillahunty and Jen Peeples during Episode 669 of The Atheist Experience and YouTube user ZJemptv amongst others.