Born Martin Robert Coles in Boston, Massachusetts on October 12, 1929, to Philip Coles, an immigrant from Leeds, England, and Sandra Young Coles, originally from Sioux City, Iowa. Robert Coles attended Boston Latin School where he played tennis, ran track, and edited the school literary magazine. He entered Harvard College in 1946, where he studied English literature and helped to edit the undergraduate literary magazine, The Advocate. He graduated magna cum laude and earned Phi Beta Kappa honors in 1950. He originally intended to become a teacher or professor, but as part of his honors thesis, he interviewed the poet and physician William Carlos Williams, who promptly persuaded him to go into medicine.

He studied medicine at Columbia University College of Physicians and Surgeons, graduating in 1954. After residency training at the University of Chicago, Coles moved on to psychiatric residencies at Massachusetts General Hospital and McLean Hospital in Belmont, MA. Knowing that he was to be called into the U.S. Armed Forces under the "doctors' draft," Coles joined the Air Force in 1958 and assigned the rank of Captain. His field of specialization was psychiatry, his intention eventually to subspecialize in child psychiatry.

He served as chief of neuropsychiatric services at Keesler Air Force base in Biloxi, Mississippi, and made frequent trips into New Orleans. During these trips he witnessed scenes of racial conflict, many of them related to the desegregation of the public schools. He wrote a series of articles for The Atlantic Monthly, profiling Ruby Bridges, one of the first Black children to desegregate a public elementary school in New Orleans and therefore a target of daily public protests, intimidation, and even death threats. As a child psychiatrist, he had volunteered to support & counsel Ruby and her family during this difficult period. These articles led to his first book, Children of Crisis: A Study of Courage and Fear, and ultimately to his decision to develop that book into a series of books documenting how children and their parents deal with profound change, a series that won him the Pulitzer prize in 1973. In 1995 he returned to his original material and wrote The Story of Ruby Bridges, a popular children's book, published by Scholastic Corporation.

He has authored more than eighty books and 1300 articles, nearly all of them centrally concerned with human moral, spiritual, and social sensibility and reasoning, mainly in children but also in adults, writers especially, including the novelist Walker Percy (who dedicated his last novel, The Thanatos Syndrome, to Coles), the poet William Carlos Williams, writer James Agee, novelist Flannery O'Connor, and others, such as Dorothy Day, Dietrich Bonhoeffer, Simone Weil, and Dorothy Lange.

Upon his honorable discharge from the Air Force, Coles returned briefly to Boston. On July 4, 1960, he married Jane Hallowell, a graduate of Radcliffe College and a high school teacher of English and history. After finishing his child psychiatry training at the Children's Hospital, the Coleses returned to the South, living in New Orleans. In addition to continuing work with children in New Orleans and Atlanta, Coles began writing non-technical articles for a number of national publications, including The Atlantic Monthly, The New Republic, Saturday Review and The Times of London. By 1969, Coles was writing in-depth profiles for The New Yorker and contributing regular columns to The New Republic, New Oxford Review, America, and the American Poetry Review.

At the urging of Erik Erikson, in 1963 Coles became affiliated with University Health Services at Harvard as a research psychiatrist, and gradually he began teaching in the Harvard Medical School, eventually becoming Professor of Psychiatry and Medical Humanities in 1977. He has taught courses in various schools across Harvard University, including the Faculty of Arts and Sciences, the Business School, the Law School, the Extension School, and the School of Education, where in 1995 he was given a newly established position as James Agee Professor of Social Ethics. He came to teach courses not only in the moral, spiritual, and social sensibilities of children but also in those phenomena generally, especially as expressed in stories, both literary fictions and oral narratives, and as affected by conditions of poverty and social injustice. As a longtime professor, Coles has influenced generations of Harvard undergraduates and graduate students. In 2007, Harvard University named an annual Call of Service lecture in honor of Coles.

His work has been recognized with numerous awards, including election to the American Academy of Arts and Sciences in 1971, a Pulitzer Prize for General Non-Fiction in 1973 for his series of books Children of Crisis, a MacArthur Award in 1981, the Presidential Medal of Freedom in 1998, and the National Humanities Medal in 2001. He later co-founded the magazine DoubleTake which documented the lives of ordinary people with photographs, articles, essays, poetry, and short stories. The magazine won several awards, including the 1998 National Magazine Award for Editorial Excellence in the category of General Excellence.

Many of Coles' works draw heavily on quoted conversations with ordinary people, as well as insights from prominent thinkers and leaders ... often people Coles has encountered personally in his career ... such as William Carlos Williams, Dorothy Day, Walker Percy, William Shawn, Anna Freud, Paul Tillich, Erik Erikson, and Robert F. Kennedy.Starting with the Children of Crisis series, Coles’ approach to his subjects involves a difficult balancing act at the heart of the documentary enterprise. His methods combine techniques of participant observation (tape recordings, field notes, drawings, etc.), clinical interpretation, academic social research, and literary narrative. Coles has never been diffident about the economic, social, and racial injustices he has observed in the field. He is a spokesperson for his subjects, a sounding board for their public voices. Coles describes his own literary methods and goals as an effort “to blend poetic insight with a craft and unite ultimately the rational and the intuitive, the aloof stance of the scholar with the passion and affection of the friend who cares and is moved.” (The Mind’s Fate, p. 10)

In a 2003 review of Coles' book on musician Bruce Springsteen, music critic David Hajdu questioned Coles' reports of the opinions on Springsteen held by various people:

:The fact that William Carlos Williams and Walker Percy had such extensive conversations with Robert Coles on the subjects of the New Jersey pop singers Frank Sinatra and Bruce Springsteen, and that those discussions yielded insights so parallel and neatly suited to Coles's own take on Springsteen is incredible--utterly incredible. I was not there to overhear them, of course, and it is impossible to check with Williams and Percy, or with the late Erikson and Shawn, whom Coles's other deceased sources quotes in his book's opening sections. But I did ask Will Percy about the comments on Springsteen that Coles attributes to his uncle, and he called them "outrageous." Walker Percy "definitely didn't talk like that," according to his nephew.

While “the facts of his subjects’ lives are indisputable,” one Coles’ scholar cautions that “some distortion is perhaps inevitable given Coles’ method and purposes and expectations of his readers. The portraits are not written as true documentary accounts of the lives of his subjects but are presented as composite views of many [subjects] designed to highlight certain features of American social life neglected in other accounts of the poor. And if they are not true, neither are they false. In some respects . . . they have the status of fiction based very firmly on the transcription of life. They examine the range of human possibility beyond category and social stereotype. . . .” (Steven Weiland, Intellectual Craftsmen: Ways and Works in American Scholarship. New Jersey: Transactions Publishers (1991): 86.