Pittsburgh took the opening kickoff and moved down the field on a 71-yard scoring drive, with Ben Roethlisberger completing a 38-yard pass to Hines Ward and a 21-yard strike to Heath Miller, putting the ball at the Arizona 1-yard line. On third down, Roethlisberger appeared to score on a quarterback scramble, but it was overruled by a replay challenge, which determined that he was down before the ball crossed the goal line. Rather than make another attempt at a touchdown, Pittsburgh settled for a Jeff Reed 18-yard field goal to take the 3–0 lead. It was the second straight year a team took the opening kickoff down for a score as the Giants did the same in Super Bowl XLII (the last time before that was the Falcons in Super Bowl XXXIII). The Steelers quickly forced an Arizona punt and then drove back down the field for what would turn into more points. On the first play of their drive, Roethlisberger completed a 25-yard pass to Santonio Holmes. Following three more completions to Miller for 26 yards and another one to Holmes for 7, reserve running back Gary Russell went into the end zone for a 1-yard touchdown run to make the score 10–0 on the second play of the second quarter. They became the first team to score on its first two drives since the Denver Broncos in Super Bowl XXXII. On defense, Pittsburgh held Arizona to just one drive and one first down in the first quarter, while gaining 135 yards.

The Cardinals got going for the first time midway through the second quarter as a 45-yard completion from Kurt Warner to Anquan Boldin moved the ball to the Steelers' 1-yard line. On the next play, Warner nearly fell over after taking the snap, but he regained his balance and threw a 1-yard touchdown pass to tight end Ben Patrick. After an exchange of punts, Roethlisberger threw a pass that was tipped at the line of scrimmage and intercepted by linebacker Karlos Dansby at the Steelers 34-yard line with 2:46 left in the half. Seven plays later, the Cardinals drove to a first down on the Pittsburgh 1-yard line. But with 18 seconds left, Warner's pass was intercepted in the end zone by linebacker James Harrison, who then took off down the sideline for the longest play in Super Bowl history, a 100-yard return for a touchdown, increasing the Steelers' lead to 17–7 at halftime. A booth review was called to verify that Harrison had broken the plane, as he was tackled at the goal line, and the ruling stood.

After forcing a punt, the Steelers started off the third quarter with another long scoring drive. Aided by three personal foul penalties against Arizona, they moved the ball 79 yards in 14 plays and took 8:39 off the clock. However, they were unable to get into the end zone, despite two first downs inside the Cardinals 10 (a penalty against Arizona on a Steelers field goal attempt gave them another chance), and they had to settle for another Reed field goal to give them a 13-point lead, 20–7. After a few more punts, Warner led the Cardinals down the field on an eight-play, 87-yard scoring drive that took 3:57 off the clock, utilizing a no huddle offense. With 7:33 left in the game, Warner threw a high floating pass to Larry Fitzgerald, who made a leaping catch through tight coverage by Ike Taylor for a touchdown, making the score 20–14.

Later on, Ben Graham's 34-yard punt pinned the Steelers back at their own 1-yard line. Two plays later on third down and 10, Roethlisberger threw a 20-yard pass to Holmes, but center Justin Hartwig was called for holding in the end zone, which not only nullified the catch, but gave the Cardinals a safety, raising the score to 20–16. Taking over on their own 36 after the free kick, Arizona took two plays to score, as Warner threw a pass to Fitzgerald on a post route. Fitzgerald caught the ball without breaking stride and took off down the middle of the field past the Steelers secondary for a 63-yard touchdown reception, giving Arizona their first lead of the game, 23–20.

The final play of the gamePittsburgh got the ball back on their own 22-yard line with 2:37 left in the game and two timeouts remaining. On their first play, a holding penalty pushed them back 10 yards. Roethlisberger then completed two passes to Holmes for 27 yards. After an 11-yard reception by Nate Washington and a 4-yard run by Roethlisberger, he completed a 40-yard pass to Holmes at the Cardinals 6-yard line. Two plays later, Holmes caught a pass in the corner of the end zone and managed to land his toes down right before falling out of bounds for a touchdown. After a booth review, the touchdown pass stood. Reed's ensuing extra point made the score 27–23 with 35 seconds remaining. Following the ensuing kickoff, Warner completed a 20-yard pass to Fitzgerald and a 13-yarder to J. J. Arrington, moving the ball to the Steelers 44. With 18 seconds left, Warner prepared to attempt a Hail Mary pass, but linebacker LaMarr Woodley forced a fumble while sacking Warner, which defensive end Brett Keisel recovered, giving the ball back to Pittsburgh with five seconds left. Roethlisberger took a knee, sealing the Steelers' NFL record sixth Super Bowl title.

Super Bowl XLIII Statistics
Scoring summary
PIT – Jeff Reed 18 yard field goal. PIT 3–0
PIT – Gary Russell 1 yard run. PIT 10–0
ARI – Ben Patrick 1 yard pass from Kurt Warner. PIT 10–7
PIT – James Harrison 100 yard interception return. PIT 17–7
PIT – Jeff Reed 21 yard field goal. PIT 20–7
ARI – Larry Fitzgerald 1 yard pass from Kurt Warner. PIT 20–14
ARI – Holding penalty on Justin Hartwig in end zone for safety. PIT 20–16.
ARI – Larry Fitzgerald 64 yard pass from Kurt Warner. ARI 23–20.
PIT – Santonio Holmes 6 yard pass from Ben Roethlisberger. PIT 27–23

Final Score
Pittsburgh Steelers - 27
Arizona Cardinals - 23

Super Bowl XLIII MVP Santonio Holmes Pittsburgh Steelers
Santonio Holmes, who caught nine passes for 131 yards and a touchdown, including four receptions for 71 yards on the final game-winning drive, was named Super Bowl MVP. He became the sixth wide receiver to win the award, and also was the third Pittsburgh receiver to win the award, following Lynn Swann and Hines Ward.