Reid, a Classics major at Princeton University, served as a naval officer, taught, and held various positions before working for The Washington Post. At the Post, he covered congress and four Presidential election campaigns, and was chief of the Posts London and Tokyo bureaus. He has also taught at Princeton and the University of Michigan. His experiences in Japan led him to write Confucius Lives Next Door: What Living in the East Teaches Us About Living in the West, which argued that Confucian values of family devotion, education, and long-term relations, which still permeate East Asian societies, contributed to their social stability. He is now the Posts Rocky Mountain Bureau Chief. A 2007 Kaiser Family Foundation media fellow in health, he is a member of the board of the Colorado Coalition for the Homeless and the University of Colorado Medical School.

His 2008 documentary for the U.S. television series Frontline, Sick Around the World, looked at the comprehensive health care systems of five developed economies from around the world. The first two countries visited were the United Kingdom and Japan, where he had previously lived, worked, and also received medical care. They were followed by Germany, Taiwan, and Switzerland.

Frontline asked Reid to follow up with a companion documentary, Sick Around America, which aired March 31, 2009, on PBS. However, Reid parted company with PBS before the film was finished when his conclusion, quoted by Russell Mokhiber in CounterPunch that "You can't allow a profit to be made on the basic package of health insurance," was omitted from the program. Instead, Reid argued that the film came off as supporting mandated private-insurance coverage. Reid was quoted as saying "...mandating for-profit insurance is not the lesson from other countries in the world. I said I'm not going to be in a film that contradicts my previous film and my book." PBS responded to these criticisms, stating that "Frontline takes a strongly different view of the characterization of its editorial disagreement with T.R. Reid as presented by Reid and Russell Mokhiber." It argued that Reid had misrepresented the role of a key respondent in the film, the extent of Reid's role in making the film, and the balance PBS had sought to present. Reid used his right of reply to challenge PBS's characterization of their and his own position.

His investigations into health care resulted in his New York Times bestselling book The Healing of America: A Global Quest for Better, Cheaper and Fairer Health Care.