Barnicle graduated from Boston University in 1965, and began working for Robert F. Kennedy. He was a speechwriter for John Tunney, Edmund Muskie, and Sargent Shriver. Barnicle appeared in the Robert Redford film, The Candidate. Barnicle then was asked to write a column in the Boston Globe, which ran for 24 years between 1974 and 1998.

The paper and its columnist won praise with their coverage of the political and social upheaval that roiled Boston after the city instituted a mandatory, court-ordered school desegregation plan in the mid-1970s. In his Pulitzer Prize-winning book, A Turbulent Decade in the Lives of Three American Families, (1986), J. Anthony Lukas wrote that Barnicle gave voice to the Boston residents who had been angered by the policy. Lukas singled out Barnicle's column and interview with Harvard psychiatrist and author Robert Coles as one of the defining moments in the coverage. The paper earned the 1975 Pulitzer Prize for public service. ("Busing Puts Burden on Working Class, Black and White" published in The Boston Globe, October 15, 1974.)

Over the next three decades, Barnicle became a dominant voice in New England. His columns mixed pointed criticism of government and bureaucratic failure with personal stories that exemplified the everyday struggles to make a living and raise a family. Tapping into a rich knowledge of local and national politics, Barnicle had unique takes on the ups and downs of luminaries such as Sen. Ted Kennedy, Sen. John Kerry, longtime Congressional Speaker of the House Thomas Tip O'Neill, as well as Boston mayors Kevin White, Ray Flynn and Tom Menino. In subsequent years, Barnicle's coverage expanded, as he reported from Northern Ireland on the conflict and resolution there to the beaches of Normandy, from where he wrote about the commemorations of World War II veterans.

Barnicle has won local and national awards for both his print and broadcast work over the last three decades, including from the Associated Press, United Press International, National Headliners and duPont-Columbia University. He holds honorary degrees from the University of Massachusetts and Colby College.

In 1998, Barnicle resigned from the Boston Globe amid allegations of plagiarism about two of his columns.The first column dated from October 8, 1995. The column recounted the story of two sets of parents with cancer-stricken children. When one of the boys, a black child, died, the parents of the other boy, a white child who had begun to recover, sent the dead child's parents a check for $10,000 USD. When the Globe could not locate the people in the story, who had not been publicly identified, Barnicle insisted nonetheless that the story was true. He said he did not obtain the story from the parents but from a nurse, whom he declined to identify. Walter V. Robinson, a Pulitzer Prize-winning editor then in charge of the Globe's "Spotlight" investigative team, failed to match a recorded death with the date of death claimed for the child.

The second column, more than 80 lines of humorous observations dated August 2, 1998, contained observations from the 1997 book Brain Droppings by George Carlin. After Barnicle said he had never read the book, the editor of the Globe issued a temporary suspension. However, WCVB-TV subsequently aired a video clip of Barnicle recommending the book to viewers, the editor called for his resignation; this was rescinded under fire from readers and the suspension period doubled instead.

Soon afterward, the New York Daily News and the Boston Herald recruited Barnicle to write for them. Barnicle told reporters that he had nothing but “fond feelings for 25 years at the Globe." Globe sports columnist Dan Shaughnessy served as a regular commentator and guest host on Barnicle’s daily radio program on WTKK. Until recently, Barnicle was on the radio three times a week with Barnicle's View, on Monday, Wednesday and Friday at 6:55am and 8:55am [1].

Barnicle has since become a staple on MSNBC, including on Morning Joe and Hardball with Chris Matthews, as well as specials on breaking news topics.