At the University of Notre Dame, Bettis finished his career with 337 rushing attempts for 1912 yards (5.7 yards per rushing attempt avg.), and made 32 receptions for 429 yards (13.4 yards per reception).

Bettis was picked in the first round (10th overall) of the 1993 draft by the Los Angeles Rams. A star even in his rookie year, he rushed for 1429 yards in 1993, and was named Offensive Rookie of the Year. He rushed for over 1,000 in his second season with the Rams but his carries declined as he fell out of favor with the team.

After Rams head coach Chuck Knox retired and was replaced by Rich Brooks, Bettis was traded to Pittsburgh in 1996.

Bettis became an integral part of the Steelers offense. Bettis was a dependable 1,000-yard rusher until 2001. Although age had slightly reduced his role, he remained important to the Steelers and was the NFL's 5th leading all-time rusher. He was named to the Pro Bowl in 1993, 1994, 1996, 1997, 2001, and 2004. Bettis won the NFL Comeback Player of the Year award in 1996, and in 2002 he was the recipient of the Walter Payton Man of the Year Award. He was

For his long career in the NFL, and his status as a native of Detroit, Jerome Bettis was awarded the key to the city of Detroit.

In February 2006, NBC Sports announced that Bettis had been signed as a studio commentator for NBC's new Football Night in America Sunday night pregame show. He is an avid bowler and has several perfect (300) games to his credit. In April, the International Bowling Museum & Hall of Fame announced Bettis would be the first inductee into its Celebrities Bowling Hall of Fame.