Humphrey attended Kilgore High School in Kilgore, Texas. He played high school football at quarterback and halfback. He was a teammate of Larry Hickman. He also lettered in baseball.
Humphrey attended and played college football at Baylor University, where he was an All-Conference player at quarterback. He scored the winning touchdown on a quarterback sneak in Baylor's 1957 Sugar Bowl victory. In 1958, he led the nation with 112 completions for 1,316 yards. In one game he passed for 387 yards and 5 touchdowns against Rice University, which was a school record that stood until 2006.
At the conclusion of his senior season, he played in the December 1958 North–South Shrine Game, where he had 5 touchdown passes and was named MVP, and the January 1959 Senior Bowl, where he was a co-captain of the South team.
In 2006, Humphrey was inducted into the Baylor Sports Hall of Fame.
Humphrey was selected by the Los Angeles Rams in the second round (16th overall) of the 1959 NFL Draft, as result of a trade with the Washington Redskins. He was a backup quarterback (only one start) for the Rams during the 1959 and 1960 seasons. On November 8, 1961, he was waived to allow him to join the Dallas Cowboys.
In 1961 he joined the Dallas Cowboys, to replace an injured Don Meredith. He appeared in 2 games and completed one pass for 16 yards. He was released on September 11, 1962.
On June 7, 1963, he was traded by the Cowboys to the St. Louis Cardinals in exchange for tight end Hugh McInnis, where he was a backup quarterback for three seasons. In 1965, he started 3 games (all loses). He was released on August 15, 1966.
On August 30, 1966, he was signed by the Denver Broncos of the American Football League on a tryout basis. He was cut on September 12.
On September 13, 1966, he was signed by the American Football League's Houston Oilers. He played in one season as a backup, starting one game.
After his professional football career was over, Humphrey had a very successful career as a high school football coach and educator. He served as head coach, principal and athletic director for Kilgore High School. He was a coach for Daingerfield, Victoria Stroman and Longview Pine Tree high school. He also was purchasing director at Kilgore Junior College.
On April 21, 1988, Humphrey died in Gregg County, Texas.