McCoughtry scored 28 points and Louisville advanced to its second straight regional semifinal with a 62-52 victory over LSU on Tuesday night.
Candyce Bingham added 17 points for the third-seeded Cardinals (31-4), who ended sixth-seeded LSU's bid to reach an unprecedented sixth straight Final Four.
Allison Hightower scored 21 for the Lady Tigers (19-11), who saw their streak of NCAA tournament victories on their home floor snapped at 12.
With five new starters and one senior on the roster, LSU was not expected to contend for another Final Four. There was even doubt in midseason whether the Lady Tigers would make the tournament before their late-season six-game winning streak.
When they qualified, they were automatically slated to open at home because Baton Rouge had been selected as a host site for the first two rounds long in advance.
LSU defeated Wisconsin-Green Bay in the first round and kept Louisville within single digits for most of the game with the help of the Lady Tigers' lone senior, Kristen Morris, who scored 13 points.
The competition was ferocious, with bodies crashing to the floor on numerous possessions. Becky Burke ended up with a bleeding gash on her lip after colliding with Latear Eason while the two hustled for a loose ball in the second half. Burke was dazed by the collision, lying on the court for several minutes while trainers attended to her.
Burke returned to drain a 3-pointer, which gave Louisville a 54-47 lead with 5:13 to go and stirred the Cardinals' bench into a frenzy.
Louisville finally went up by double digits when McCoughtry's steal and fast-break layup with just over a minute to go made it 62-51. McCoughtry then tilted her head back and let out a yell as she high-stepped back on defense.
McCoughtry struggled with her shot at times going 9-of-22 and 0-of-5 from 3-point range, but hit 10-of-11 free throws.
With every victory, Louisville sets a new school record for wins in a season. The Cardinals still need one more to give their program a new first: a berth in the regional finals. Louisville lost to North Carolina in the regional semifinals in New Orleans last season.
In the first round, Louisville had used its trapping defense to force Liberty into 27 turnovers, but LSU was much more prepared for the Cardinals' defensive pressure.
With two guards moving in tandem as LSU brought the ball up the floor, the Lady Tigers effectively broke Louisville's trap. The Lady Tigers' only real trouble was hitting shots. LSU made only four of their first 13, but trailed only 12-10 thanks to strong defensive play.
Turning the ball over only once through the first 19 minutes, LSU pulled ahead 17-16 on Katherine Graham's baseline jumper. Morris followed with another baseline jumper, then Hightower added free throws and a jumper near the top of the key during a 9-2 run that put the Lady Tigers up 23-18.
The crowd, overwhelmingly in LSU's favor, was energized. Louisville showed no panic, instead turning to the two players who'd led the Cardinals all season. McCoughtry and Bingham combined for all points in a 9-0 run late in the half, highlighted by Bingham's layup as she was fouled, and the Cardinals surged into the lead, 29-25.
Bingham scored 11 in the first half and McCoughtry 16, including a pair of free throws to put Louisville up 33-29 at halftime.