Majors was born in the Detroit suburb of Wyandotte, Michigan. Parents Carl & Alice Yeary were both killed in separate car accidents (prior to his birth and when he was one year old respectively) and at age two, Majors was adopted by an uncle and aunt, Harvey and Mildred Yeary, and moved with them, and their biological son, Bill, to Middlesboro, Kentucky.

Since his adoptive older brother had been a football star in school, Majors tirelessly committed himself to the sport. While a student at Middlesboro High School, he participated in many sports from track to football. He graduated in 1957, went to Indiana University,then transferred to Eastern Kentucky University in Richmond, Kentucky, in 1959.

After college, he received an offer to try out for the St. Louis Cardinals football team. Instead, he moved to Los Angeles and found work at the Los Angeles Park and Recreation Department as the Recreation Director for North Hollywood Park.

In LA, Majors met many actors and industry professionals, including Dick Clayton, who suggested he attend his acting school. After one year of acting school, Clayton felt that Majors was ready to start his career. At this time, he picked up the stage name Lee Majors as a tribute to childhood hero Johnny Majors.

At age 25, Majors landed his first, although uncredited, role in "Strait-Jacket" (1964), which starred Joan Crawford. After appearing in a 1965 episode of "Gunsmoke," he starred as Howard White in an episode of The Alfred Hitchcock Hour, “The Monkey’s Paw - A Retelling,” based on the short story by W. W. Jacobs later the same year.

Majors got his big break when he beat out over 400 young actors, including Burt Reynolds, for the co-starring role of Heath Barkley in a new ABC western series, "The Big Valley." During the series, Majors co-starred in the 1968 Charlton Heston film "Will Penny," for which he received an "Introducing" credit, and landed the lead role in "The Ballad of Andy Crocker" (1969), a made-for-television film which was first broadcast by ABC. When "The Big Valley" was cancelled in 1969, he signed a long-term contract with Universal Studios. In 1970, Majors joined the cast of "The Virginian" for its last season.

In 1971, he landed the role of Arthur Hill's partner, Jess Brandon, on "Owen Marshall: Counselor at Law," which garnered critical acclaim during its three seasons on ABC. In one episode, his then girlfriend, Farrah Fawcett, guest-starred.

Majors' co-starring role on Owen Marshall led him to a starring role as Colonel Steve Austin, an ex-astronaut with bionic implants in "The Six Million Dollar Man," a 1973 television movie broadcast on ABC.

In 1974, the network decided to turn it into a weekly series. The series became a huge international success, being screened in over 70 countries, turning Majors into one of the leading pop icons of the 70's, and, along with his then wife Farrah Fawcett, who herself was soon to become a leading pop icon of the 70's, into one of Hollywood's high-profile power couples with both appearing on the cover of magazines everywhere.