After playing college football with the Arizona State Sun Devils, he was selected in the first round of the 1978 NFL draft by the San Diego Chargers.

He was traded to the Green Bay Packers after a contract dispute with the Chargers, and later finished his playing career with the Cleveland Browns.

After graduating from Franklin D. Roosevelt High School in the Oak Cliff neighborhood of Dallas, Jefferson received a scholarship to attend Arizona State University.

A consensus All-American selection in 1977 and two-time All-Western Athletic Conference pick, Jefferson concluded his career with an NCAA record 42 consecutive games with a reception.

He, along with Charlie Joiner, Kellen Winslow and Wes Chandler (who replaced him on the Chargers) represented one of the most potent receiving corps of the early 1980s, known as Air Coryell.

[5] On November 12 against the Kansas City Chiefs, Jefferson caught a 14-yard touchdown pass with no time remaining while slipping in a wet end zone for a 29–23 overtime victory.

[14][16] In a September 14, 1980, overtime game against the Oakland Raiders, played in San Diego, Jefferson out-leaped Lester Hayes for a throw from Dan Fouts.

[19] On September 17, 1981, the Chargers traded Jefferson to the Green Bay Packers after he stated the day before that he could not play for San Diego.

With the Packers, Jefferson starred opposite future Pro Football Hall of Fame wideout James Lofton.

Jefferson, Lofton, and tight end Paul Coffman teamed up with quarterback Lynn Dickey to give the Packers one of the most explosive passing attacks in the NFL at the time; however, a defense which hovered near the bottom of the league relegated Green Bay to three 8-8 finishes and a second-round playoff appearance during the strike-shortened 1982 season.

[28] Jefferson became an assistant coach at the University of Kansas and was the director of player development for the Washington Redskins until the end of the 2008–2009 season.