Humphrey was
drafted out of Tennessee State University in the first round of the
1968 NFL draft with the third overall choice by the Falcons. He had been well prepared as a defensive lineman at TSU by coach Merritt and defensive coordinator
Joe Gilliam Sr. In his Falcons' rookie year (1968), Humphrey started every game, had 11.5 sacks, recovered three fumbles, and was named the
NFL's Defensive Rookie of the Year. Even after an excellent rookie season, Humphrey knew he had to expand his technique and skill set to continue his success in the NFL. He credited the Falcons' new 1969 defensive coordinator,
Marion Campbell, with helping him branch out to obtain that knowledge, leading to his continued success. The 25th ranked offense was so poor, however, it scored only 179 points, and the team finished with a 7–7 record. Humphrey temporarily retired after four games in 1978, because of the team's perpetual lack of success; going to work for
WAOK radio station in Atlanta, where he had The Claude Humphrey Show. Humphrey finished out his career with the Philadelphia Eagles from 1979 to 1981. During Super Bowl XV, when Humphrey was called for roughing the passer against
Oakland Raiders quarterback
Jim Plunkett, he picked up the penalty flag and fired it back at referee
Ben Dreith. He finished his career with an unofficial 122,
All-Pro and Pro Bowl honors Humphrey's stellar career included being named first-team
All-Pro five times (1971/NEA, 1972/AP, 1973/AP, 1974/NEA,1977/NEA), second-team All-Pro four times (1969/AP, 1970/NEA, 1974/AP, 1977/AP), when Humphrey unofficially recorded a Falcons career-high or career-high 14½ == Pro Football Hall of Fame ==