Born in Norfolk, Virginia in 1931, Lefty attended Granby High School and was selected to the All-State basketball team. He attended college at Duke University from 1950 to 1954. Soon after college, he returned to Granby High School and was promoted to varsity coach in 1956. In 1957, he became the head coach at Newport News High School, where he compiled a 57-game winning streak. Driesell then served as the head coach at Davidson College from 1960 to 1969.
In 1969, he was hired by the University of Maryland, where at his introductory press conference, he made the bold statement that he wanted to make Maryland the "UCLA of the East." While not UCLA, he did lead the Terrapins to eight NCAA Tournament appearances, a National Invitation Tournament championship, two Atlantic Coast Conference regular season championships, and one Atlantic Coast Conference tournament championship. Maryland also attained a No. 2 Associated Press ranking during four consecutive seasons from 1972 to 1976.
Driesell coached the Maryland Terrapins from 1969 to 1986. During his tenure, he successfully recruited numerous exceptional players, including Tom McMillen, Len Elmore, John Lucas, Albert King, Buck Williams, and Len Bias.
In 1974, he signed perhaps the best college prospect of his career, Moses Malone, but Malone chose instead to go to a professional basketball franchise, the Utah Stars. Malone was the first player in the modern era to proceed directly from high school into professional basketball,deciding on the day classes were scheduled to begin. At Maryland, Driesell began the now nationwide tradition of Midnight Madness. According to longstanding NCAA rules, college basketball teams were not permitted to begin practices until October 15. Driesell traditionally began the first practice with a requirement that his players run one mile in six minutes, but found that the players were too fatigued to practice effectively immediately afterwards. At 12:03 a.m. on October 15, 1971, Driesell held a one-mile run at the track around Byrd Stadium, where a crowd of 1,000 fans had gathered after learning of the unorthodox practice session. The event soon became a tradition to build excitement for the basketball team's upcoming season.
Lefty later coached at James Madison and Georgia State compiling a career record of 786-394. He was elected to the College Basketball Hall of Fame in 2007.