[13] After starting the season with a loss to the Iowa Hawkeyes, Roethlisberger led the Miami RedHawks to an unbeaten record in the MAC, 12 consecutive wins, a #10 ranking in the Associated Press poll, and a 49–28 victory over Louisville in the 2003 GMAC Bowl.

[34] All three would enjoy lengthy and successful careers with the teams that signed them and have been compared favorably to the aforementioned 1983 Draft, which included Hall of Fame quarterbacks John Elway, Jim Kelly, and Marino.

[43] Maddox's injury changed the Steelers' original plan for Roethlisberger, which was for him to sit on the bench or play sparingly during the first season or two in order to learn the team's system.

[49] On October 31, he had one of his biggest games, leading the Steelers to a 34–20 victory over the defending Super Bowl champion and previously undefeated New England Patriots, ending their NFL-record 21-game winning streak.

One interception was returned for a touchdown, and the other was thrown with 2:03 left in the fourth quarter, which set up a potential game-winning field goal by Jets kicker Doug Brien.

[61] Their second road win came on January 15 when Roethlisberger led the Steelers against the Indianapolis Colts in the Divisional Round, the NFL's top team throughout the season and a heavy favorite to represent the AFC in Super Bowl XL.

Roethlisberger threw for 197 yards and recorded a game-saving tackle on Colts' defensive back Nick Harper, who had just recovered a Jerome Bettis fumble with less than two minutes left in the game.

Pittsburgh led early but had to survive a Colts comeback to win 21–18, after an errant call that the NFL later admitted was a mistake,[62] which overturned a Troy Polamalu interception that would have secured the game for the Steelers.

[77] In Week 11, Roethlisberger overcame three first-half interceptions by throwing for 224 yards and two touchdowns in the fourth quarter, leading the Steelers to score 21 points and come back to beat the Cleveland Browns, 24–20.

[83] Roethlisberger ended the season on a good note by defeating the Cincinnati Bengals by a score of 23–17 in overtime and eliminating them from playoff contention in what was Bill Cowher's final game as the Steelers' head coach.

[90] Pittsburgh was hit with a torrential storm, delaying the Monday night game 30 minutes due to lightning, while turning the new sod on the field, laid earlier that week, into a soggy mess.

[92] In Week 16 against the St. Louis Rams, Roethlisberger became the first quarterback in NFL history to have two perfect passer rating (158.3) games in the same regular season, completing 16 of 20 passes for 261 yards and three touchdowns.

[107] The next week, Roethlisberger threw for 239 yards in the first half—a career-high for one half—and directed the game-winning drive, passing for an eight-yard touchdown to Hines Ward to defeat the Jacksonville Jaguars by a score of 26–21.

[116] After a LaMarr Woodley strip sack and a fumble recovery by Brett Keisel, Roethlisberger and the Steelers offense went back on the field to kneel the ball and run the clock out, ensuring Pittsburgh's victory.

[132] In Week 7 against the Miami Dolphins, with the Steelers trailing, 22–20, with 2:37 remaining in the game, Roethlisberger was at the center of controversy when he ran a QB draw and dove for the end zone, appearing to score a touchdown in the process.

[137] Roethlisberger passed for a season-high 387 yards and 3 touchdowns in the Week 10, 39–26 loss, to the New England Patriots, but also had an interception returned for a score and was sacked five times as he tried to rally the Steelers from a 23–3 deficit in the second half.

Roethlisberger completed a deep pass to rookie wide receiver Antonio Brown for 58 yards and Rashard Mendenhall's rushing touchdown put the Steelers ahead for good, 31–24, with 1:33 left.

[146] In Super Bowl XLV against the Green Bay Packers, Roethlisberger was hit as he attempted a pass to Mike Wallace in the first quarter, and it was intercepted for a touchdown by Nick Collins.

After falling behind, 28–17, in the fourth quarter, Roethlisberger threw a 25-yard touchdown pass to Mike Wallace, and then pitched the ball to Antwaan Randle El on an option run for the two-point conversion to make it 28–25.

Taking over at his own 13 with 1:59 left and down 31–25, Roethlisberger was unable to lead the game-winning drive against Green Bay this time after his pass fell incomplete to Wallace on 4th and 5 at his own 33-yard line, ensuring the only Super Bowl loss of his career.

[157] In Week 13 against the Cincinnati Bengals, Roethlisberger moved past Terry Bradshaw in the Steelers' record books; first for most times sacked, then for most pass completions in team history.

Baltimore went on to win their final game and secured the division title, leaving Steelers with the number 5 seed to face Denver in the Wild Card round of the playoffs.

Despite the heroic efforts of Roethlisberger and company, Tim Tebow's magical season continued with his best single-game performance to date, capped off with an 80-yard completion to Demaryius Thomas to end overtime after one play.

[171] Roethlisberger became the second member of the Steelers in less than a year to return to college and complete his degree, with teammate Polamalu doing the same thing the previous off-season during the 2011 NFL lockout.

[234] On December 19, 2017, Roethlisberger was named to his fourth consecutive and sixth career Pro Bowl along with his star receiver Antonio Brown and three of his starting offensive lineman among others.

The show eventually evolved into having guest interviews with current and former players and coaches such as Kenny Pickett, Jerome Bettis, Bill Cowher and Mike Tomlin.

[335] Roethlisberger was traveling east on Second Avenue when a 1996 Chrysler New Yorker made a left turn in front of the motorcycle on the South Tenth Street Bridge[336] when the accident occurred.

area of the nightclub, encouraged them to take shots of alcohol before Anthony Barravecchio – an off-duty Coraopolis, Pennsylvania policeman, undercover DEA narcotics officer at Pittsburgh International Airport, and one of Roethlisberger's bodyguards[357][358] – claimed he led her down a hallway and left.

[363] Blash later admitted denigrating the accuser and never formally questioning Roethlisberger; he did speak to the NFL player and his off-duty police bodyguards at the Capital City club.

For instance, the Pittsburgh restaurant chain Peppi's sells the "Roethlisburger", at a price of $7.00, in correlation with his jersey number "7", and also having ingredients that describe his playing style (scrambled eggs for "scrambler", beef and sausage for his size and strength).