Reynolds' parents were Burton Reynolds, who was of Cherokee and Irish ancestry, and his wife, Fern Miller. Reynolds states in his autobiography that his family was living in Lansing when his father was drafted into the United States Army. Reynolds, his mother and his sister joined his father at Fort Leonard Wood, where they lived for two years. When Reynolds's father was sent to Europe, the family returned to Lansing, Michigan. In 1946, Reynolds moved to Riviera Beach, Florida, with his parents. His father, Burt Sr., later became Chief of Police of Riviera Beach. Riviera Beach is the next town north of West Palm Beach.

In his senior year at Palm Beach High School, Reynolds was named First Team All State and All Southern as a fullback, and received multiple scholarship offers. After graduating from Palm Beach High School in West Palm Beach, Florida, Reynolds attended the Florida State University on a college football scholarship, and played halfback. Reynolds hoped to be named to All-America teams and to have a career in professional football. In the first game of the season Reynolds was injured, and a car accident later that year worsened the injury. With his college football career ended, Reynolds considered becoming a police officer, but his father suggested that he finish college and become a parole officer. In order to keep up with his studies he began taking classes at Palm Beach Junior College (PBJC) in neighboring Lake Worth, Florida. In his first term at PBJC Reynolds was in a class taught by Watson B. Duncan III. Duncan pushed Reynolds into trying out for a play he was producing, Outward Bound. He cast Reynolds in the lead, based on his impressions from listening to Reynolds read Shakespeare in class. Reynolds won the 1956 Florida State Drama Award for his performance in Outward Bound. Reynolds calls Duncan his mentor and the most influential person in his life.

The Florida State Drama Award included a scholarship to the Hyde Park Playhouse, a summer stock theater, in Hyde Park, New York. Reynolds saw the opportunity as an agreeable alternative to more physically demanding summer jobs, but did not yet see acting as a career. While working at Hyde Park, Reynolds met Joanne Woodward, who helped Reynolds find an agent, and be cast in Tea and Sympathy at the Neighborhood Playhouse in New York City. Reynolds received favorable reviews for his performance in Tea and Sympathy. Reynolds then went on tour with Tea and Sympathy, driving the bus as well as appearing on stage.

After the tour Reynolds returned to New York and enrolled in acting classes. His classmates included Frank Gifford, Carol Lawrence, Red Buttons and Jan Murray. After a botched improvisation in acting class, Reynolds briefly considered returning to Florida, but he soon got a part in a revival of Mister Roberts, with Charlton Heston as the star. After the play closed, the director, John Forsythe, arranged a movie audition with Josh Logan for Reynolds. The movie was Sayonara, and Reynolds was told he couldn't be in the movie because he looked too much like Marlon Brando. Logan advised Reynolds to go to Hollywood, but Reynolds did not feel confident enough to do so.

Reynolds worked odd jobs while waiting for acting opportunities. He waited tables, washed dishes, drove a delivery truck and worked as a bouncer at the Roseland Ballroom. It was while working as a dockworker that Reynolds was offered $150 to jump through a glass window on a live television show.

He made his Broadway debut in Look, We've Come Through. Reynolds first starred on television with Darren McGavin in the 1959-1961 NBC series, Riverboat. In 1960-1961, he appeared in two episodes of the syndicated series The Blue Angels, about elite fliers of the United States Navy. That same season, he guest starred in the syndicated crime drama, The Brothers Brannagan in the episode "Bordertown". Reynolds went on to appear in a number of other shows, including a role as blacksmith/ de facto deputy, and half-Native American Quint Asper on CBS's Gunsmoke from 1962–1965. On June 11, 1959, he appeared as Tony Sapio with Ruta Lee as Gloria Fallon in the episode entitled "The Payoff" of NBC's 1920s crime drama, The Lawless Years. In 1962 Reynolds secured a guest appearance on Perry Mason in "The Case of the Counterfeit Crank".

His film debut was in 1961, in the movie Angel Baby. At the urging of friend Clint Eastwood, Reynolds used his TV fame to secure leading roles in overseas low budget films, commonly called "Spaghetti Westerns". (Eastwood advised Reynolds from experience, as he had done the same). Reynolds first Spaghetti Western, Navajo Joe, came out in 1966. These low budget starring roles established Reynolds as a bankable leading man in movies, and earned him starring roles in American big-budget motion pictures. During this period, he starred in two short-lived cop shows: Hawk and Dan August. He disparaged these shows, telling Johnny Carson that Dan August had "two forms of expression: mad and supermad." His breakout performance in Deliverance in 1972 made him a star. The same year, Reynolds gained notoriety when he posed naked in the April (Vol. 172, No. 4) issue of Cosmopolitan Magazine.

Reynolds claims he was offered the role of James Bond by producer Albert R. Broccoli, after Sean Connery left the franchise. Reynolds turned the role down, saying "An American can't play James Bond. It just can't be done." In 1973, he released the album Ask Me What I Am. He would also sing with Dolly Parton in The Best Little Whorehouse in Texas.

Reynolds appeared on ABC's The American Sportsman hosted by outdoors journalist Grits Gresham, who took celebrities on hunting, fishing, and shooting trips around the world.

On March 15, 1978, Reynolds earned a star on the Hollywood Walk of Fame, and in the same year built a dinner theatre in Jupiter, Florida. His celebrity was such that he drew not only big-name stars to appear in productions but sell-out audiences as well. He sold the venue in the early 1990s, but a museum highlighting his career still operates nearby.