UofL (15-5, 5-2), which entered the game 15th nationally in field goal percentage defense (37.7 percent per opponent), put the clamps on the Red Storm. The Cards held St. John's to 32.1 percent shooting (17 of 53), recorded a season-high 14 steals and forced 17 turnovers, which they turned into 30 points.
"With the exception of the end, I thought we played very good defense," said Louisville coach Rick Pitino, whose team led by as many as 22 points before the Red Storm rallied late.
It was the 11th time this season UofL has held an opponent to under 40 percent shooting, and the fifth time the Cards have done it in the last six games.
Meanwhile Williams, the 6-foot-6 junior forward from Seattle, flirted with another triple-double - tallying eight points, eight rebounds and eight assists - but almost ended up with a not-so-good quadruple-double because he also racked up seven turnovers.
"I thought Andre McGee and Derrick Caracter played exceptional tonight," Pitino said.
Their performances helped offset a one-man show by Anthony Mason Jr. The St. John's junior forward, and son of the former NBA player of the same name, scored 29 points on 10 of 21 shooting, including 7 of 11 from three-point range. He also grabbed nine rebounds. The rest of the Red Storm, though, were a combined 7 of 32 from the field.
"Anthony Mason Jr.'s a tough guy to guard," Pitino said. "He played really good, made some tough shots and we gave a nice birthday present to him. It wasn't as much our defense and his brilliance on offense."
The Cards were good on both offense and defense in the first half.
Louisville led 35-20 at halftime thanks to 46.2 percent shooting from three-point range (6 of 13) and because the Cards' defense caused problems for the Red Storm. UofL forced nine turnovers and turned those into 18 points - outscoring St. John's 18-3 in points off turnovers in the first half.
Louisville jumped out to a quick 11-3 lead - hitting three quick threes.
"Louisville is a very, very good team and they have so many weapons and an score in so many ways, we thought starting out playing some zone and we did a good job of playing it early and then they started spreading it out and getting it to the high post," said St. John's coach Norm Roberts, whose team started two freshmen and played six.
"David Padgett is a terrific passer and Derrick Caracter is so big and strong inside and hard to handle in there, so we had to go to man-to-man and put in a smaller lineup. They did a terrific job. I thought we battled, but we are just so young."
But the Red Storm (7-11, 1-6) reeled off seven straight points - five by Mason Jr. The Cards answered with a 14-2 run sparked by T-Will, who hit two threes during the surge after sitting out for two minutes. He finished the first half with seven points, five assists and three rebounds while Smith led Louisville with 10 points.
Mason Jr. had 14 points on 5 of 9 shooting, but St. John's hit just 26.1 percent (6 of 23) from the field in the first half as the rest of the Red Storm was 1-for-14.
UofL increased its lead to 17 points early in the second half, but the Red Storm stormed back. St. John's scored nine of the next 10 points to cut the Cards' lead to seven (41-34). But UofL ran off 11 straight points - on back-to-back three-pointers by Juan Palacios and Andre McGee and two baskets by Caracter inside. The second of those was part of an old-fashioned three-point play that gave Louisville its largest lead to that point (52-34) with just under 10 minutes to play.
"We had to buckle down on D," McGee said.
The Cards cruised from there, force-feeding the ball inside to Caracter.
"DC played really well today," Padgett said. "He did a good job of getting position in the post."
UofL, which has won 10 of its last 12, will play at Connecticut at 7 p.m. Monday.
"They're playing as well as anybody in the conference right now, maybe the country," Padgett said of the team that upset Indiana on Saturday.
Added Pitino: "I'm excited about this win, we're playing real good basketball right now and we're going to have to be to play a team like Connecticut."