Teddy Bridgewater threw for 250 yards with a touchdown and Senorise Perry ran for a pair of scores as seventh-ranked Louisville came away with a 27-13 victory over Kentucky at Commonwealth Stadium.
Bridgewater completed 16-of-28 passes and Perry added 100 yards on 11 carries for the Cardinals (3-0), who took a step up in competition after opening the season with easy home routs of Ohio and Eastern Kentucky.
"It's a big game because it's a rival game and there's so much put into it," said Louisville coach Charlie Strong. "That's what I told our players, all games are big games but this game is a little different and that's why we had to go out and go prepare the way we did. Just make sure we had the focus and we had the confidence to believe that we could come in here and beat them."
Louisville entered the game averaging 545 yards offensively, mostly through the air, but the ground game accounted for 242 yards on Saturday -- more than 100 yards over the Cardinals' average of 138.5 through two games.
In addition to Perry, Michael Dyer ran for 62 yards on 11 carries and Dominique Brown added 45 yards on 12 attempts. Bridgewater also scrambled six times for 35 yards.
Jalen Whitlow threw a touchdown pass for Kentucky (1-2), which was coming off a 41-7 win over Miami-Ohio last week. The Wildcats finished with 376 total yards, but turned it over three times and suffered a third straight loss to their Bluegrass State rivals.
"Disappointed with the loss," said Kentucky coach Mark Stoops. "I was proud of our guys' effort. I felt like we fought, played tough at times, had our opportunities. Disappointed that we didn't make the plays when we needed to.
"Give credit to Louisville. They made the plays when they needed to."
Louisville carried only a 10-3 lead to the intermission, but started the third quarter with an 83-yard touchdown drive. Bridgewater connected on four passes for 49 yards and Perry ripped off a 27-yard run before scoring from the one to make it 17-3.
Whitlow had the Wildcats in Louisville territory on the ensuing series, but was picked off at the goal line by Charles Gaines. The Cardinals followed with a march into Kentucky territory, aided by consecutive Bridgewater completions of 47 and 24 yards, but it stalled inside the five and John Wallace kicked a 21-yard field goal for a 20-3 advantage.
A 47-yard run by the Wildcats' Jojo Kemp on the first play after the next kickoff set up a 30-yard Joe Mansour field goal that trimmed Kentucky's deficit to 14 in the first minute of the fourth quarter.
Perry then put the game out of reach with a 36-yard TD scamper to cap another 83-yard Louisville possession.
Kentucky managed to score once more, as Whitlow threw a 3-yard touchdown pass to Alex Montgomery with 6:21 remaining, then drove into Louisville territory in the closing two minutes before Whitlow was sacked on fourth down.
Whitlow finished 8-of-17 for 105 yards and added 37 yards on the ground in defeat. Maxwell Smith -- the pocket passer in Kentucky's quarterback rotation -- finished 9-of-20 for 109 yards, while Kemp ran for 80 yards on five carries.
Louisville turned a Whitlow fumble into three points just over five minutes into the contest, as Marcus Smith recovered at the Kentucky 27 and Wallace booted a 36-yard field goal for a 3-0 lead.
The Cardinals were moving late in the first quarter, but DeVante Parker fumbled after a reception and Kentucky took over at its own 41. The Wildcats converted the turnover into a 37-yard Mansour field goal to knot the score.
Louisville finally reached the end zone with 2:36 remaining in the half, when Bridgewater hit Parker with a 13-yard pass to cap an 11-play, 52-yard drive.
Kentucky answered with a lengthy march, but Smith fumbled inside the Louisville 15 and Preston Brown recovered for the Cardinals with 43 seconds to play in the half.
Louisville finished with 492 total yards ... Kentucky still leads the all-time series, 14-12, including an 8-8 mark in Lexington.