Luke Hancock's third 3-pointer of the second half put Louisville ahead to stay in the final minute and the 10th-ranked Cardinals pulled out a 58-53 win over No. 12 Syracuse at the Carrier Dome.
Hancock hit four from beyond the arc overall and finished with 12 points for Louisville (24-5, 12-4 Big East), which has won five straight and avenged a 70-68 home loss to Syracuse in January.
"It's big," Hancock said of the victory. "This was like a tournament game. It was that kind of atmosphere."
Louisville was No. 1 when the Orange scored the final four points to steal that game. This time, the Cardinals took it from Syracuse (22-7, 10-6) in the final minute.
Hancock drilled a three from the left wing with 53 seconds left to snap a 48-48 tie and the Orange couldn't answer.
Michael Carter-Williams, who led Syracuse's charge back from a seven-point deficit, missed badly on a 3-point try and Russ Smith hit two from the line to extend the Louisville lead to five. The Orange then turned it over and Kevin Ware made a free throw with 23 seconds to play.
Brandon Triche canned two from the line with 16 seconds left to pull Syracuse within four and the Orange nearly came up with a steal on the inbound pass but lost the ball out of bounds. Louisville successfully inbounded the ball and Ware made two more free throws to restore a six-point margin before C.J. Fair drained a three with five seconds remaining.
Smith was fouled immediately and calmly sank two from the stripe to seal it. The junior led Louisville with 18 points.
Fair scored 19 points to lead Syracuse, which has lost three in a row for the first time since a four-game skid from Jan. 17-29, 2011. The Orange have also dropped two straight at the Carrier Dome after having their 38-game home winning streak stopped last Saturday with a loss to Georgetown.
James Southerland scored 13 points for Syracuse and Carter-Williams finished with 11 points, seven rebounds and six assists in defeat.
"We had the lead. We just lost it at the end," Southerland said. "We just have to have the mentality that when we have the ball, we're not going to lose it."
Hancock answered Southerland's third triple of the second half with one of his own for a 39-38 Louisville lead with nine minutes left, and the Cardinals sharpshooter drilled another three with 5 1/2 minutes remaining to cap a 6-0 run to make it 47-40.
Syracuse answered with the next eight, the first six from Carter-Williams before a jumper from Fair gave the Orange a 48-47 edge with 2:52 remaining. After a couple of empty trips, Smith made one free throw to tie it with 1:39 left.
Smith hit a three on Louisville's first possession, but the Cardinals missed their next seven shots while Syracuse scored seven straight points. The Cardinals then answered with nine in a row and maintained the lead until the Orange tied it at 13-13.
Smith, though, canned another shot from beyond the arc with just over eight minutes left in the half to put Louisville back on top and the Cardinals took their biggest lead of the half a little over four minutes later when a lob from Peyton Siva to Chane Behanan made it 23-17. The only points in the final 3 1/2 minutes came on a Fair layup that left Syracuse down by four at the break.
A three by Southerland 4 1/2 minutes into the second half gave Syracuse a 30-28 lead. He hit another from beyond the arc three minutes later for a 35-33 edge and found the range again with just over nine minutes left to put the Orange ahead 38-36.
Gorgui Dieng scored 11 points and grabbed 14 rebounds for Louisville, notching his eighth double-double of the season and the 20th of his career ... Ware finished with eight points in the victory ... The Cardinals limited Syracuse to just 35.7 percent from the field, the 18th time this season a Louisville opponent has failed to reach 40 percent ... Triche scored eight points and accounted for seven of Syracuse's 16 turnovers ... Syracuse freshman center DaJuan Coleman returned to action for the first time since undergoing knee surgery on Jan. 29 ... Syracuse had won three straight against Louisville. The Cardinals now lead the all-time series, 14-7.