Lawrence scored the Red Storm's first 12 points of the game and he had 14 at halftime as the Cardinals took a 32-28 lead despite St. John's shooting just 25 percent (5-for-20).
The Red Storm (9-6, 2-2 Big East) didn't need much from Lawrence in the second half as the other starters began to hit shots. St. John's made eight of its first 13 shots in the second half, outscoring Louisville (13-4, 1-3) 19-7 to take a 47-39 lead with 11:07 to play.
Louisville, which lost for the third time in five games, couldn't get any offense going in the second half, especially without leading scorer Taquan Dean, who missed his second of three games with an ankle injury.
St. John's extended the lead to as much as 64-48 with 3:33 to go on a layup by Lawrence.
Lamont Hamilton had 15 points for St. John's, including a 3-pointer and a three-point play in the 10-3 run that made it 47-39.
Anthony Mason Jr. had 14 points and 11 rebounds for St. John's, while guard Daryll Hill, playing his second game after missing four with a knee injury, had nine points and 10 rebounds.
St. John's, which leads the Big East in points allowed at 56.7 per game, outrebounded Louisville 41-26 and held the Cardinals 17 points below their average.