An offensive assistant at both the collegiate and professional levels, he held coordinator positions in the National Football League (NFL) with the Washington Redskins in 2003, the Atlanta Falcons in 2007, the Oakland Raiders in 2010, and the Cincinnati Bengals from 2014 to 2015.

[5] Jackson, a native of Los Angeles, was a quarterback at Dorsey High School in his hometown, where he also lettered in basketball.

[11] In the spring of 1991, he coached the running backs, receivers and special teams for the World League’s inaugural year champion London Monarchs.

[14] Jackson served as University of Southern California's offensive coordinator from 1997 to 2000, helping to recruit and develop players, including quarterback Carson Palmer, with whom he was later reunited in Cincinnati and Oakland.

[15][16] Jackson also held three NFL summer coaching internships, in 1990 with the Los Angeles Rams, 1992 with the Phoenix Cardinals and 1995 with the Washington Redskins.

In 2005, the Johnson-Houshmandzadeh tandem combined to total 175 receptions for 2,388 yards, while helping the team secure the AFC North title and a playoff berth for the first time in 15 years.

[24][25] In 2007, after leaving Cincinnati, Jackson was an NFL offensive coordinator for the second time when he served in that capacity for the Atlanta Falcons under Bobby Petrino and interim head coach Emmitt Thomas.

[30][31] After the 2010 season, Jackson was named head coach of the Oakland Raiders in 2011, succeeding Tom Cable.

[32] Jackson was fired by the Raiders on January 10, 2012, after one season as head coach, by new general manager Reggie McKenzie.

[34] The Bengals finished 10–6 in 2012 and made the playoffs, losing in the wild card round to the Houston Texans on the road.

[42] On October 29, 2018, the Browns announced that they had fired Jackson, who had amassed a record of 3–36–1 during his tenure with the team, including a 2–5–1 start to the 2018 season.

He said that he was "lied to" by Browns owner Jimmy Haslam regarding the state of the franchise and the team's impending rebuild that took place following his firing.

He also said he received a one-year contract extension halfway through the Browns' 0-16 campaign in 2017 that the team decided not to make public.

[53] In June 2024, Jackson was hired to be the assistant general manager of the Georgia State Panthers football team.