After attending the University of Nevada, Las Vegas, he was selected in the second round of the 1985 draft by Philadelphia Eagles, with whom he remained through the 1995 season. During the latter years his relations with Ray Rhodes, then the Eagles' head coach, became strained, and he announced his retirement from football following the end of that season, taking a job as an analyst for TNT in 1996. The following year, however, he resumed his playing career, with the Minnesota Vikings from 1997 through 1999, the Dallas Cowboys in 2000, and the Baltimore Ravens in 2001 before retiring for good. He won the NFL MVP award in 1990, the height of the 'Ultimate Weapon' stories, and again after his comeback with Minnesota in 1998.

Cunningham attended Santa Barbara High School. As a senior, he led his team to a League title and the CIF Finals.

Cunningham had been the Eagles second-round pick in 1985. In his rookie season he played sparingly as a backup to veteran Ron Jaworski but made a splash with his uncanny scrambling ability, though he completed just 34 percent of his passes and threw just one touchdown against eight interceptions. In 1986, new head coach Buddy Ryan arrived in Philadelphia and made wholesale changes, many of them unorthodox. At the quarterback position, Ryan designated 35-year-old Ron Jaworksi the starter but would replace the aging veteran with the fleet-footed Cunningham in third-and-long situations where the youngster's scrambling would presumably put the defense on its heels. After a hand injury to Jaworski in week 10, Cunningham would replace him as the Eagles' starter. Cunningham was permanently handed the Eagles starting job for the 1987 season.

Cunningham would on occasion exhibit sensational feats of athleticism, perhaps most notably in a 1988 game on Monday Night Football against the NY Giants. Linebacker Carl Banks torpedoed in and crunched the Eagles quarterback at the midriff for a seemingly sure tackle. Cunningham managed to twist his body in midair, put a hand down for balance while parallel to the ground, regain his footing, and pass to tight end Jimmie Giles for a touchdown. The following season, Randall uncorked a 91-yard, into-the-wind punt to clinch a key game against the Giants. Another highlight staple was in a 1990 game against the Buffalo Bills, when Cunningham, throwing from his end zone, was about to be engulfed from the blind side by Bruce Smith. Randall ducked under the flying tackle and heaved a pass 60 yards off his back foot, resulting in an unforgettable 95-yard touchdown. That same year, Cunningham finished with 942 rushing yards - 2nd most ever for a Quarterback, 10th best in the league, and nearly became the first quarterback to both run and pass for 1,000 yards in a season.