Patrick Patterson and John Wall added 17 points each for the Wildcats (15-0), who matched their best start in 40 years by breaking a two-game losing streak to the Cardinals.
Edgar Sosa and Jerry Smith led Louisville (10-4) with 11 points apiece but the Cardinals shot just 32 percent and couldn't contain Wall when it mattered.
The freshman star shook off a slow start by scoring six straight points during a decisive 14-3 run late in the second half after the Cardinals had surged to the lead.
Louisville coach Rick Pitino was booed lustily early by the record Rupp Arena crowd, but the crowd quickly moved on after the Cardinals erased a 13-point deficit.
Louisville pulled in front 42-41 on a free throw by Terrence Jennings with 9:51 remaining before Wall went to work.
He hit a tough leaner along the baseline to put Kentucky back in front then added a pull-up jumper to extend the lead to three. He stripped the ball from Louisville's Peyton Siva and knocked down a pair of free throws after being fouled trying to finish on the break.
Perry Stevenson added a reverse layup, Ramon Harris drilled a 3-pointer and Patrick Patterson converted a three-point play to give Kentucky a 55-45 lead with 5:35 to go.
Louisville kept scrapping but would get no closer than seven the rest of the way.
Pitino and former friend turned friendly rival John Calipari shook hands briefly as the horn sounded, both coaches only too happy to put one of the most contentious meetings in the series' long history behind them.
The teams combined for 51 personal fouls -- including five technicals -- and 37 turnovers in a game that made up for in passion what it lacked in precise play.
Calipari said before the game he wasn't sure if his young team understood the magnitude of the rivalry.
The Wildcats were whistled for a pair of fouls on Louisville's first possession, the calls kick starting a series of trash talking shoving matches that kept the referees busy.
Things grew more heated moments later when Cousins and Louisville forward Jared Swopshire got tangled up battling for a loose ball. Louisville's Reginald Delk came over and gave Cousins a push while Swopshire tried to wiggle free.
All three players received technical fouls for unsportsmanlike conduct, but Cousins may have dodged a bullet when replays showed he appeared to throw an elbow at Swopshire's head during the scrum.
Cousins stayed in the game long enough to score Kentucky's first six points as the Wildcats swarmed the shaky Cardinals into bad shots and turnovers.
Louisville missed 18 of its first 19 shots and looked overwhelmed by the electric atmosphere.
Kentucky was hardly better. Wall, looking mortal for the first time all season, couldn't get going against the myriad of defenders the Cardinals threw at him.
Kentucky led just 27-19 at the break before Louisville briefly got into a rhythm behind Sosa and Smith. Yet it wasn't enough as the smaller Cardinals wore down over the final 7 minutes against the tallest team in the country.
The Wildcats outscored Louisville 40-24 in the paint, with Cousins dominating his matchup with Louisville center Samardo Samuels. Samuels finished with nine points and nine rebounds, turned it over three times and was muscled out of the way by Cousins.
Cousins kept his emotions in check for the most part and capped the win with a thunderous dunk with 37.2 seconds left that put the Wildcats up 68-57 as the crowd erupted.
Calipari had urged fans to behave themselves, and for the most part they obliged.
Security officials confiscated any signs they deemed inappropriate, though the crowd made sure to remind Pitino of his troubling summer when he admitted to having an affair six years ago with a woman later charged with trying to extort him for millions.
During one timeout in the first half a group in the upper deck chanted the woman's name, though Pitino was too busy yelling at Sosa to notice.