It was the most points allowed by North Carolina, surpassing a 66-0 loss to Virginia in 1912. Louisville's nine touchdowns was also a record for North Carolina, which has fielded teams since 1888.
Louisville defensive end Elvis Dumervil had three sacks, two forced fumbles and his first career interception, and Michael Bush added three touchdowns for the Cardinals (4-1), who scored on their first eight possessions and topped 60 points for the fourth straight home game.
On the opening drive, Bush capped a nine-play march with a 3-yard TD run. Louisville scored on the game's opening possession for the 13th time in 26 games under coach Bobby Petrino.
The Tar Heels (2-3) immediately answered, going 79 yards in 6:18, their longest touchdown drive of the season in possession time. Running back Ronnie McGill, seeing his first action since tearing a chest muscle this summer, scored on a 2-yard run to tie the score.
The Tar Heels' offense sputtered after that, gaining only 72 yards the rest of the half.
Bush had 28 rushing yards on Louisville's next drive, then caught a short pass from Brohm and weaved for a 13-yard touchdown.
On North Carolina's next possession, Matt Baker threw a short pass to a surprised Dumervil, who barreled to the Tar Heels' 8. Bush overthrew Brohm at the goal line on a trick play before Art Carmody booted a 20-yard field goal.
Two pass interference penalties kept alive Louisville's next drive and Bush scored again with 9:55 left in the half.
The Tar Heels marched to the Cardinals' 26, but the drive stalled after an illegal motion penalty and two incompletions by Baker. Connor Barth then hooked a 44-yard field-goal try, typifying the Tar Heels' day.
On Louisville's next play, Brohm double-pumped and hit Mario Urrutia in stride for a 73-yard touchdown. Brohm added a 39-yard TD pass to Montrell Jones in the final minute of the second quarter and finished the half 13 of 15 for 255 yards.
The Cardinals' 38 first-half points were more than the Tar Heels had allowed in a game this season - and things go no better in the second half.
Wallace Wright fumbled the opening kickoff and Carmody kicked a 42-yard field goal to send Louisville over 40 points for the 16th time in Petrino's three seasons.
Baker left the game with a twisted ankle on North Carolina's next possession and Brohm tossed a 2-yard TD pass to Scott Kuhn for a 48-7 lead.
The Cardinals punted for the first time in the opening minute of the fourth quarter.
Baker returned, but Dumervil jarred the ball loose on his third sack. Earl Heyman picked up the fumble and went 31 yards for a score. Dumervil leads the nation with 15 sacks.
Backup running back George Stripling had a short touchdown run to push Louisville over 60 points for the sixth time under Petrino.