Johnson attended Chabot College in California from 2004 to 2005 before transferring to Kentucky. In his first season with the program, he recorded 12 catches for 159 yards (13.3 avg) and 1 touchdown. Against Clemson in the Music City Bowl, Johnson had three receptions for 67 yards.
The 2007 season was a historic one for Johnson as he compiled 61 receptions for 1,052 yards (17.2 avg) and 13 touchdowns. He became the fourth player in school history to gain over 1,000 yards receiving and his thirteen touchdowns in a season rank second on the school's season-record list.
Johnson was drafted by the Buffalo Bills in the seventh round (224th overall) of the 2008 NFL Draft.
Battling a severe rib injury, Johnson only managed 2 catches for 10 yards in the 2009 season.
He had a breakout campaign in 2010 with 82 receptions, 1073 yards and 10 touchdowns. Following the season, Johnson was named the 2010 Vizio Top Value Performer for being the NFL player who outplayed his salary by the widest margin.
During the 2011 season, Johnson was fined twice for excessive celebrations. The first was Week 12 against the New York Jets. Johnson pretended to shoot his leg and then fly like a Jet and pretended to crash, imitating Jets receiver Plaxico Burress. The second was during Week 17 against the New England Patriots, after scoring a touchdown, he lifted his jersey to reveal "Happy New Year!" written on his under-shirt. He was given a 15-yard unsportsmanlike penalty, and head coach Chan Gailey subsequently benched Johnson for the rest of the game, ending his season.
In the 2012 season, staying consistent with his statistics, he recorded 79 receptions for 1,046 yards and 6 touchdowns. He became the only receiver in Buffalo Bills history to record three consecutive 1,000 yard receiving seasons.
In 2014, he showed off his multiple tattoos for PETA's "Ink not Mink" anti-fur campaign.
On March 17, 2015, Johnson signed a three-year, $12 million contract with the San Diego Chargers. Johnson had a fast start to 2015, but was hampered by recurring injuries later through the season. He finished the season with 45 receptions for 497 yards and 3 touchdowns.
On August 10, 2016, it was reported that Johnson would be out for the entirety of the 2016 season after having surgery to repair his meniscus.
On March 7, 2017, Johnson was released by the Chargers.
