Nicknamed "the Bus" due to his large size and forceful running style, he played college football for the Notre Dame Fighting Irish and was selected 10th overall by the Los Angeles Rams in the 1993 NFL draft.

A six-time Pro Bowl and two-time first-team All-Pro selection, he is regarded as one of the greatest power runners of all time and ranks eighth in NFL rushing yards.

New coach Rich Brooks instituted a more pass-oriented offense, a major reason why Bettis was limited to 637 yards,[15] a significant dropoff from his 1993 and 1994 totals.

Morris eventually pleaded guilty to marijuana possession and was cut by the team in June 1996, leaving Bettis as the featured back.

Bettis does hold the Steelers' franchise record for rushing yards in a single season when including postseason play.

Bettis was leading the league with 1,072 rushing yards in 2001 when he suffered a serious hip and groin injury that sidelined him for the remainder of the regular season.

But when an injury took Staley out of action midway through the year, Bettis stepped in and gained 100-plus yards in six of the next eight games, and in seven consecutive starts.

Bettis spent the 2005 season as a short-yardage running back, but managed two notable games along the way: a 101-yard, two-touchdown effort in a pivotal week 14 win over Chicago (his second-to-last game in Pittsburgh) in which he ran over Bears' safety Mike Green and the NFL's Defensive Player of the Year linebacker Brian Urlacher on the goal line during a heavy snow squall.

During a Thanksgiving Day game with the Detroit Lions on November 26, 1998, he was sent out as the Steelers representative for the overtime coin toss.

[23] During that 2004 season, Bettis and New York Jets running back Curtis Martin dueled for position on the all-time rushing yards leaderboard.

[26] Shortly after the Steelers lost the 2004–2005 AFC Championship game to the eventual Super Bowl XXXIX champion New England Patriots, Ben Roethlisberger approached Bettis.

When Bill Cowher pulled Bettis from the game late in the fourth quarter, he was given a standing ovation from the Steeler fans.

Bettis contributed 52 yards and a touchdown in the Steelers' wildcard playoff victory over the Cincinnati Bengals on January 8.

After their wildcard win, Ben Roethlisberger revealed to the team that he promised to Bettis that he would get him to the Super Bowl, in order to get him to come back for the 2005 season.

On January 15, 2006, Bettis was the center of one of football's most memorable[29] endings in a divisional playoff game against the Indianapolis Colts.

As Bettis ran towards the end zone, Colts linebacker Gary Brackett popped the ball out of Jerome's hands, where, in seemingly another occurrence of the Sports Illustrated "cover jinx," it was picked up by cornerback Nick Harper, who was stopped from returning the fumble all the way for a touchdown by Steelers quarterback Ben Roethlisberger.

Bettis delivered a rousing speech to his teammates the day before the game, asking them to "Just get me to Detroit", his hometown, where Super Bowl XL was to be played.

[30] Bettis's wish was granted, as he and the Steelers advanced to Super Bowl XL with a 34–17 win over the Broncos, led by Ben Roethlisberger's arm.

Hines Ward, the MVP of the game, said during the Super Bowl commercial, "I'm going to Disney World and I'm taking The Bus!"

Before the Steelers' home opener of the 2006 NFL season, a large school bus drove onto the field, and Bettis stepped out to a massive crowd ovation.

He was one of several Steelers players being honored as part of the celebration of the franchise's five Super Bowl victories; Lynn Swann and Franco Harris were also present.

In April 2006, Bettis and his parents teamed up with Don Barden, the head of PITG Gaming LLC, in a bid for a casino on Pittsburgh's Northside to be called the Majestic Star.

Signing autographs at a paper convention, Michael Scott tries to invite him to a room party, which Bettis declines.

[46] Bettis returned to NBC to help Bob Costas preside over the Vince Lombardi Trophy presentation at the end of Super Bowl XLIX on February 1, 2015.

Bettis starred in a Geico commercial in 2019, playing a running back in flag football that dominates the competition (49–0).

Bettis portrays himself in the episode "Welcome to the Ex-Files" in Season 4 of the CBS comedy series The Neighborhood, where he visits the home of principal characters Calvin and Tina Butler for dinner after running into them at a restaurant.

In the course of the evening, characters learn that Bettis & Tina had a "summer fling" when they were teenagers, triggering jealousy in Calvin that gets resolved by the end of the episode.

Bettis returned on campus at the University of Notre Dame in 2021–2022 to finish his bachelor's degree, something he had started nearly 30 years earlier.

[47] On March 29, 2008, Bettis accompanied Barack Obama on a campaign visit to the U.S. Steel plant in Braddock, Pennsylvania.