Dick Gregory grew up poor and fatherless from St.Louis Missouri, one of six children. His family was supported by his mother who worked on the side as a maid in addition to welfare benefits the family received. As described in his autobiography Nigger, things were rough for the Gregory family. They were nearly destitute, going without necessitites such as electricity and running water for extended periods of time. As a child, Gregory was very ashamed of his family condition and it made him a target for teasing by other kids. He began using comedy as a way of disarming their attacks. Dick was a poor student but excelled at running and this talent, coupled with the assistance of dedicated high school teachers like Warren St.James earned him a track scholarship to Southern Illinois University Carbondale. A track star there, his college career was interupted by Uncle Sam, as he left college to spend two years in the U.S. Army. The military was were he got his start in comedy, entering and winning several Army talent shows at the urging of his commanding officer who noticed his penchant for joking. After his military service, he performed as a comedian in small, primarily black nightclubs. He worked for the United States Postal Service during the daytime. In 1961, he was hired by Hugh Hefner, to work with the Chicago Playboy Club. This is where he began to gather fame. He used the following line to wow an entirely white audience, prompting Hefner to hire him:

Good evening ladies and gentlemen. I understand there are a good many southerners in the room tonight. I know the South very well. I spent twenty years there one night. Last time I was down South I walked into this restaurant and this white waitress came up to me and said, "We don't serve colored people here." I said, "That's all right. I don't eat colored people. Bring me a whole fried chicken." Then these three white boys came up to me and said, "Boy, we're givin' you fair warnin'. Anything you do to that chicken, we're gonna do to you." So I put down my knife and fork, I picked up that chicken and I kissed it. Then I said, "Line up, Boys!" In a few years he was known nationally, appearing on television; his autobiography, Nigger, was a best selling book in America, selling 7 million copies. He became more involved in struggles for civil rights, activism against the American War in Vietnam, economic reform, anti-drug issues, conspiracy theories, and others. As a part of his activism, he went on several hunger strikes.

Dick Gregory unsuccessfully ran for president of the United States in 1968 as a write-in candidate of the Freedom and Peace Party, which had broken off from the Peace and Freedom Party. He won 47,097 votes, which was more than the party he broke off from received. The Freedom and Peace Party also ran other candidates, including Beulah Sanders for New York State Senate and Flora Brown for New York State Assembly.

He wrote Write Me In about his presidential campaign. About one hundred Dick Gregory dollar bills (Mark Lane VP) were circulated at Operation Breadbasket in Chicago advertising their campaign. Some were passed in cash transactions and caused some trouble (and/or publicity).

In recent years he has been a figure in the health food industry.

Dick Gregory the comedian and civil rights leader became better known as Dick Gregory the nutrition guru during the 1980s. Gregory first became a vegetarian in the 1960s. He lost a considerable amount of weight by going on extreme fasts, some lasting upwards of 50 days and he began advocating for a raw fruit and vegetable diet. In the 1980s he developed a diet drink called "Bahamian Diet Nutritional Drink" and went on TV shows advocating for his diet and to help the morbidly obese. He is probably best remembered for his attempts, chronicled in the media on daytime talkshows in early 1988, at helping 1,200 pound Long Island man Walter Hudson drop nearly 600 pounds in only a few months on a liquid diet. Mr. Hudson shortly gained the weight back and later died from complications from his extreme obesity. Nonetheless Gregory claims his restrictive diet has kept him in good health and continues to advocate for a natural diet lifestyle.

In early June 2005, during the late stages of the 2005 trial of Michael Jackson, he was invited by Jackson's father, Joseph Jackson, to advise Jackson on his health. On June 4th, Gregory brought a blood-circulating machine to Jackson's house, but Jackson refused to use it.Also on February 26,2006 in Atlanta,Georgia making a speech at Soul Vegetarian he fainted will paramedics showed up soon afterwards.

Gregory married his wife Lillian in the 1960s, and they now have twelve children. As of 2005, he resides in Plymouth, Massachusetts.

At a Civil Rights rally marking the 40th anniversary of the Voting Rights Act, Gregory criticized the United States, calling it "the most dishonest, ungodly, unspiritual nation that ever existed in the history of the planet. As we talk now, America is 5 percent of the world's population and consumes 96 percent of the world's hard drugs," Gregory said.

He is number 81 on Comedy Central's list of the 100 greatest standups of all time.

He has his own star on the St. Louis Walk of Fame.

Gregory is a prominent member of Alpha Phi Alpha, the oldest intercollegiate Greek-letter fraternity established for African Americans.

Gregory appears as "Mr. Sun" in the television show Wonder Showzen (the third episode, titled "Ocean", aired in 2005). As Chauncey, a puppet character, imbibes a hallucinogenic substance, Mr. Sun warns "Don't get hooked on imagination, Chauncey. It can lead to terrible, horrible things." Gregory also provides guest commentary on the Wonder Showzen Season One DVD.