Eric Dickerson was selected second overall in the 1983 NFL Draft by the Los Angeles Rams. An immediate success, he established rookie records for most rushing attempts (390), most rushing yards gained (1,808) and most touchdowns rushing (18), including another two receiving touchdowns. His efforts earned him All-Pro, Pro Bowl, Player of the Year and Rookie of the Year honors.

In his second season, Dickerson continued his onslaught on the NFL record book becoming a member of the 2000 rushing yards club. Twelve times in 1984 he gained more than 100 yards rushing, breaking the record of 100-yard games in a season held by O.J. Simpson. His 2,105 total yards rushing beat Simpson’s 1973 NFL season record of 2,003 yards. No one has since rushed for more yards in a single NFL season. Dickerson's 5.6 yards per carry led the Rams to a playoff berth in 1984.

In 1985, he rushed for 1,234 yards while missing the first two games. He set a playoff record with 248 rushing yards against the Dallas Cowboys. 1985 marked the beginning of on-going contract disputes between Dickerson and the Rams, and after playing just three games for the Rams during the strike-shortened 1987 season, Dickerson was traded to the Indianapolis Colts in one of the NFL's biggest trades ever, a three-way deal between the Rams, the Buffalo Bills and the Colts which saw the Rams receive RB Greg Bell, three 1st round picks, the Bills receive LB Cornelius Bennett and the Colts getting Dickerson. Although he played in just nine games with the Colts that year, he still managed to gain 1,011 yards to finish the season with 1,288. Also, he spearheaded a late season Colts run that helped the team to their first winning season (and first playoff berth) in 10 years.

In 1988, Dickerson, with 1,659 yards rushing, became the first Colt to lead the league in rushing since Alan Ameche in 1955. This would mark the apogee of Dickerson's career with the Colts (although he would gain 1,311 yards rushing in 1989). In 1989 he passed the 10,000 yard mark, and was the fastest player ever to do so (91 games), accomplishing the feat faster than greats like Jim Brown (98 games), Barry Sanders (103 games), Emmitt Smith (106 games), and LaDainian Tomlinson (106 games). By 1989, he had set a new NFL record with seven straight seasons of more than 1,000 yards rushing, and led the league for four of those seasons. 1991 was his final year with the Colts.

On April 26, 1992, Dickerson was traded by the Colts to the Los Angeles Raiders for their fourth and eighth round picks in the 1992 draft. He recorded his 63rd and 64th career 100 yard games and led the team in rushing attempts and yards. The following season, Dickerson was traded to the Atlanta Falcons on July 7, 1993 for a sixth round draft pick.

Dickerson retired from the NFL as the 2nd leading rusher of all-time.

In 1999 he was selected to the Pro Football Hall of Fame.