Louisville responded later in the first quarter, when Senorise Perry capped off a 12 play, 75-yard drive with a 6-yard touchdown rush.
Pitt regained the lead early in the second quarter, when Todd Thomas blocked Ryan Johnson's punt, and ran the ball back 41 yards for a touchdown.
The Panthers went into halftime with a 21-17 lead, but that would be the last lead of the day for Pittsburgh.
The Cardinals came out of halftime and set the tone immediately. After receiving the kickoff to open the second half, Louisville quarterback Teddy Bridgewater completed a 75-yard touchdown pass to DeVante Parker, giving Louisville a 24-21 lead.
Louisville added two more touchdowns in the third quarter, both coming on Perry touchdown runs, giving the Cardinals a commanding 38-21 lead.
Pitt cut the deficit to 38-28 early in the fourth quarter, when Sunseri scored on a 1-yard touchdown rush.
The Cardinals put the game away late in the fourth quarter, when Perry scored his fourth touchdown of the game, on a 59-yard touchdown run, giving the Cardinals a 45-28 lead.
Sunseri hooked up with Devin Street on a 2-yard touchdown pass with 40 seconds left on the clock, but it was too little, too late, as the Cardinals went onto win, 45-35.
Box Score Hero: Senorise Perry. Perry scored four touchdowns, and rushed for 101 yards on just 12 carries.
Rankings Ramifications: Though it wasn't a dominant effort, Louisville will have a chance to move up in the rankings.
But Did They Cover? Louisville entered the game as two point favorites, and covered the spread.
For More On This Game: For more on Cardinals football, visit Louisville blog Card Chronicle, plus Big East blog Big East Coast Bias and SB Nation Indiana. For more on Pittsburgh football, visit Pitt blog Cardiac Hill, plus SB Nation Pittsburgh. And Big East Coast Bias, for the time being.
Next Week's Schedule: Louisville will play host to South Florida, while Pitt heads to Buffalo to take on the Bulls.