The Cardinals (24-4, 12-2 Conference USA) used a 12-0 run midway through the second half to take the lead. Although the Tigers tied the game once, they never overcame the Cardinals as Juan Palacios scored six straight points and had a block down the stretch.
Darius Washington scored 14 for Memphis (16-12, 9-5), which shot 19.6 percent for the game and hit only one of its 23 shots from outside the arc. Leading scorer Rodney Carney was scoreless, missing all nine of his shots, including four 3-pointers.
"We played spectacular defense tonight," Louisville coach Rick Pitino said. "This is the first time since I've been a coach that I was glad to have a low scoring, grind it out game. We wanted to be the better defensive team tonight."
It was a game that featured tough defense and physical play on both ends of the court, contributing to poor shooting nights all around, little offensive punch and a load of turnovers.
The game was the final regular season conference game in the heated rivalry as Louisville is leaving Conference USA after this season to join the Big East. The series dates to the mid-1960s and the Missouri Valley Conference. The two teams, who played periodically before the Valley days, also were members of the Metro Conference before the current C-USA.
They'll continue the series over the next four years, although conference bragging rights won't hang in the balance.
Memphis defeated Louisville 85-68 at Freedom Hall earlier this month, marking the Cardinals' worst home loss in the Rick Pitino era.
Louisville's revenge factor, the rivalry and a raucous crowd made for an intense night. But the first half was a rite of survival for both teams as they went to intermission tied at 23.
Louisville survived a 28-percent shooting and eight turnovers in the first half, while leading scorers -- Garcia and Larry O'Bannon -- sat on the bench with three fouls each.
Memphis was able to stay close despite even worse shooting -- 19 percent -- and missing all 12 of its 3-point shots. Carney missed all five of his first-half shots, while starting guards Washington and Anthony Rice were a combined 2-of-13.
Memphis closed the half 2-of-16 from the field, including Joey Dorsey's tip at the buzzer to tie the score.
The Tigers' poor shooting allowed the Cardinals to stay in a zone through part of the first half while their offensive threats were on the bench, preventing Washington from penetrating like he did in the earlier meeting when he scored 25 points.
That changed in the early stages of the second half as Memphis started going to the basket, building the lead to 39-28 with 9:41 left. But Louisville had a run of its own remaining, answering with 12 straight points to take the lead for good.