Keith began playing for the University of Oklahoma under Coach Barry Switzer in 1984. He assisted the Sooners to a 42-5-1 record in his four seasons and a national championship in 1985. He caught a total of 62 passes for 1,407 yards, at an average of 23.7 yards per catch, and was a College Football All-American Team selection in 1986 and 1987. In the 1986 Orange Bowl, the national championship, Keith caught a 71-yard pass from Jamelle Holieway for a touchdown, which would be the first of two touchdowns in the Sooner's victory over Penn State. He was later voted Offensive Player of the Century at OU and was elected to the College Football Hall of Fame.
In 1988, the Philadelphia Eagles selected Keith as the thirteenth pick of the first round in the National Football League draft. Keith made an immediate impact on the Eagles team and the NFL during his rookie season. He recorded 81 receptions for 869 yards and 6 touchdowns in his first season, along with 7 catches for 142 yards in the Eagles playoff game that year. He was the NFC offensive rookie of the year and the only first year player to be selected by the NFL for the Pro Bowl in Hawaii. He had a total of 242 receptions with the Eagles, for 1,909 yards and 20 touchdowns. Keith was selected to the Pro Bowl three times during his tenure with the Eagles; 1988, 1989, and 1990. He had a great connection with his teammates, especially his quarterback Randall Cunningham.
Keith played three years in sunny Miami. During his tenure there he recorded 146 receptions for 1,828 yards and 18 touchdowns. He had a great run with Dan Marino behind the ball. While with the Dolphins, he was selected to the Pro Bowl in 1992, 1993, and 1994. Keith was traded to the Green Bay Packers in March of 1995.
After being traded from the Miami Dolphins, Keith found himself trying to fit in at Green Bay. One of his best friends and former Philadelphia Eagles teammate Reggie White convinced him that Green Bay was where he was supposed to be. It wasn't long before Keith began leaving his mark at Lambeau Field and in the AFC division. During his two years with the Packers, Keith recorded 53 receptions thrown by Brett Favre for 647 yards and 11 touchdowns. In 1996, the Packers won Super Bowl XXXI, giving Keith his first Super Bowl ring. He was selected to the Pro Bowl in 1996 and retired from the Packers in 1997.