He was a medical writer at the Albany Times Union newspaper, in Albany, N.Y., from 1989 to 1994. In 1992, he was a Knight Science Journalism fellow at MIT. Following that he became director of publications at Harvard Medical School. In 1994 he co-founded a publishing company, CenterWatch, that coveredthe pharmaceutical clinical trials industry. CenterWatch was acquired by Medical Economics, a division of The Thomson Corporation, in 1998.

Articles which he cowrote won the 1998 George Polk Award for Medical Writing and the 1998 National Association for Science Writers’ Science in Society Journalism Award for best magazine article. A 1998 Boston Globe article series he cowrote on psychiatric research was a finalist for the 1999 Pulitzer Prize for Public Service.

He has written on and off for the Boston Globe and in 2001, he wrote his first book Mad in America about psychiatric research and medications, the domains of some of his earlier journalism.

Whitaker's first book stirred some emotions in the medical profession. Richard Bentall writes that one of his physician friends "felt as bruised as a sinner who had been denounced by a strident evangelical preacher" upon reading Whitaker's Mad in America.

Physician Larry S. Goldman wrote a highly critical review of the book in Medscape Today, stating that it "looks as if it were commissioned by Scientologists". Goldman writes that Whitaker "is ready to throw the baby out with the bath water" because Mad in America fails to acknowledge any biological abnormalities in schizophrenia despite the considerable literature in this area, while at the same conceding that Whitaker's argument that the true causes of schizophrenia are not known is correct. Goldman also writes that the book promotes something akin to a conspiracy theory "because it strings together many decades of disparate flops into a unifying theme of ongoing catastrophe". Goldman concludes that the "overheated style" of the book "tends to undermine some of its more important points, such as the unhealthy symbiosis between the US pharmaceutical industry and much of the psychiatric research community and the ever-present miserliness of public mental healthcare systems".

In a rejoinder to Goldman's review, physician Nathaniel S. Lehrman disagrees with Goldman, and writes that "Whitaker is right", and goes on to agree with the main points in the book, namely that antipsychotic drugs cause brain damage, that despite "psychiatrically produced misconceptions", they "do not fix any known brain abnormality nor do they put brain chemistry back into balance. What they do is alter brain functions in a manner that diminishes certain characteristic symptoms." Lehrman then writes that all the data accumulated on the neurobiology of schizophrenia "has hardly helped patient care."

In Anatomy of an Epidemic, published in 2010, Whitaker continued his work.