The Super Bowl run began on January 8, 2006 as Roethlisberger helped lead the Steelers to a Divisional Round playoff win over the Cincinnati Bengals—an AFC North rival that had beaten the Steelers by seven points in the regular season to win the division championship. The rematch featured two teams with identical records, having split their regular season series since each team won on the road. Early in the game on Carson Palmer's first throw, a tackle by former Steeler Kimo von Oelhoffen resulted in Palmer's anterior cruciate ligament (ACL) being completely torn. The Bengals' backup quarterback, Jon Kitna, came in and led the Bengals to leads of 10–0 and 17–7. However, the 17–7 lead midway through the second quarter would be the last time in the 2005 postseason that the Steelers would trail an opponent by more than three points. After Kitna failed to produce, the Steelers took advantage by taking the next 24 straight points, and the win, in a 31–17 victory in Cincinnati.
On January 22, 2006, the Steelers defeated the Denver Broncos by a score of 34–17 in Denver to win the AFC Championship and advance to Super Bowl XL. Roethlisberger completed 21 of 29 passes for 275 yards and threw two touchdown passes and scored one touchdown himself on a four-yard play-action bootleg. His run was the last touchdown of the game, sealing the win for the Steelers.
The Pittsburgh Steelers won Super Bowl XL 21–10 over the Seattle Seahawks in Detroit on February 5, 2006. Roethlisberger had one of the worst passing games of his career, completing just nine of 21 passes for 123 yards and two interceptions; his passer rating of 22.6 was the lowest in Super Bowl history by a winning quarterback. Though he did convert eight third-down situations in the game to help the Steelers win, none of them was bigger than his 37-yard pass to Super Bowl XL MVP Hines Ward on a third-and-28 that set up the Steelers' first touchdown (a one-yard quarterback sneak by Roethlisberger on third and goal). With the victory, Roethlisberger, at 23 years old, became the youngest quarterback to win the Super Bowl, a record previously held by Tom Brady of the New England Patriots.
In the Steelers Week 15 matchup against the Atlanta Falcons, Roethlisberger completed 27 of 35 passes for 360 yards in a 27–20 victory. The victory made Roethlisberger only the sixth quarterback in NFL history to have defeated at least 31 different teams, joining Tom Brady, Drew Brees, Kerry Collins, Brett Favre, and Peyton Manning; like Brady, Roethlisberger has only played with one team and thus has not played against the Steelers. The Steelers lost 41–38 in Roethlisberger's only other matchup against Atlanta in 2006, and he was suspended for the Steelers 15–9 overtime victory against the Falcons in 2010.
Roethlisberger is a spokesman for Swiss Roots, a campaign intended to help Americans of Swiss origin reconnect with their Swiss ancestral heritage. In May 2006, Roethlisberger and his family traveled to Switzerland for a week.
Upon arriving at Mercy Hospital, he went immediately into surgery, where he remained for more than seven hours. The broken bones in his face were repaired. The subsequent news conference with the hospital staff was brief but confirmed early reports that the most serious injuries were to the head and face. There was no neck, spinal, or brain damage found. After surgery, at approximately noon on June 13, 2006, Roethlisberger was upgraded to fair condition.
Roethlisberger was released from the hospital at 11:46 PM on June 14, 2006. The next day, he released a statement apologizing for concerning friends, family, all his fans, and the Steelers organization, and in which he also stated, "If I ever ride again, it certainly will be with a helmet." Roethlisberger was subsequently videotaped by KDKA-TV staff riding without a helmet on a Pittburgh freeway.
Roethlisberger gave his first television interview after the accident on July 13, with ABC's Good Morning America. He said he was told by responding paramedics that he ruptured a major blood vessel in his mouth and was minutes away from dying. Despite the seriousness of the accident, his recovery went so well that he started the first three Steelers preseason games in 2006.