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. Humphrey was an All-American in 1967. Humphrey's stellar career included being named First-team All-Pro five times, Second- Team All-Pro three times, and All-NFC six times. He was second-team All-NFC in 1976 when Humphrey unofficially recorded a career high 15 quarterback sacks. In addition Humphrey was named to the Pro Bowl six times over the span of his career. Humphrey finished out his career with the Philadelphia Eagles from 1979–81. In 1980 Humphrey was a designated pass rusher, recording a team high 14½ sacks helping the Eagles become NFC champions and earn a spot in Super Bowl XV. He finished his career with an unofficial 126½ career sacks with the Falcons and Eagles. He retired in 1981, the season before sacks were recorded as an official NFL statistic. During Super Bowl XV, Humphrey was called for roughing the passer against Oakland Raiders quarterback Jim Plunkett. Humphrey picked up the penalty flag and fired it back at referee Ben Dreith. Humphrey is a member of the Georgia Hall of Fame and the Tennessee Hall of Fame. His alma mater retired his number and inducted him into their Hall of Fame. His high school has also retired his jersey and he is a member of his high school Hall of Fame, and is a member of the Atlanta Falcons Ring of Honor. Humphrey is a member of Phi Beta Sigma.
Outside Football
Claude Humphrey also had a guest appearance on The Dukes of Hazzard episode "Repo Men" in which he portrayed Big John, a counterfeiter.
Humphrey was a final 15 candidate in 2003, 2005, and 2006. On August 27, 2008, he was named as one of two senior candidates for the 2009 Hall of Fame election. In August 2013, he was named as one of two senior candidates for the 2014 Hall of Fame election. In February 2014, Claude Humphrey was elected to the Pro Football Hall of Fame on the senior ballot. During his time in football, Humphrey was a revolutionary pass rushing defensive lineman who paved the way for Reggie White, Bruce Smith, and fellow 2014 NFL HOF inductee Michael Strahan. On August 2, 2014, Humphrey was officially inducted at the Enshrinement Ceremony where his bust, sculpted by Scott Myers, was unveiled.