Chandler accepted an athletic scholarship to attend the University of Florida in Gainesville, Florida, where he was a wide receiver for coach Doug Dickey's Florida Gators football team from 1974 to 1977. While he was a Florida undergraduate, Chandler became a member of Alpha Phi AlphaFraternity (Theta Sigma Chapter). As a Gator, he caught ninety-two passes for 1,963 yards and a school record twenty-two touchdowns in a run-oriented offense, adding six more scores on rushes and kick returns. and leading the team in receiving yards in 1975, 1976 and 1977. Chandler was a first-team All-Southeastern Conference (SEC) selection and a first-team All-American in 1976 and 1977, a first-team Academic All-American in 1977, and the recipient of the Gators' Fergie Ferguson Award as a senior team captain in 1977. He also finished tenth in the balloting for the Heisman Trophy in 1977. He is widely considered to be one of the best all-around football players to ever play for the University of Florida, and has been named to several all-time Gators and all-SEC teams, and was inducted into the University of Florida Athletic Hall of Fame as a "Gator Great" in 1989. In 2006, The Gainesville Sun recognized Chandler as No. 6 among the top 100 Florida Gators players of the first 100 years of the team.
The following season was Chandler's best, when he led the NFL with 1,032 receiving yards and nine receiving touchdowns in the strike-shortened 1982 season; his average of 129 yards receiving per game that year is still an NFL record. He also caught nine passes for 124 yards in a playoff win over the Pittsburgh Steelers. Chandler represented Chargers players in the players' union, and many NFL players in that role were cut or traded after the 1987 NFL strike. After he was elected to the union's executive committee, Chandler was traded to the San Francisco 49ers, with whom he finished his career in 1988. He played in four games before retiring in October after tendinitis in a knee and frustration over his performance. The 49ers went on to win the Super Bowl that season. "My heart wasn't in it. It had nothing to do with being a quitter. It was more about real-life decisions," he said.
During his 11-year NFL career, Chandler caught 559 passes for 8,966 yards and 56 touchdowns, rushed for 84 yards, returned 48 kickoffs for 1,048 yards, and gained 428 yards on 77 punt returns. Overall, he amassed 10,526 all-purpose yards. At the time of his retirement, Chandler ranked twelfth in NFL history in receiving yards and thirteenth in receptions. He also earned four Pro Bowl selections, including three with the San Diego Chargers. In 2001, Chandler was inducted into the San Diego Chargers Hall of Fame.