"He was far and away the best player on the floor," Gonzaga coach Mark Few said.
Standout Gonzaga guard Gary Bell Jr. sat out a second game with a broken hand. Star forward-center Sam Dower Jr. went scoreless in seven minutes off the bench after missing two games with a bruised lower back.
"Everyone had to step up a little bit," Karnowski said.
"It was probably our best all-around effort of the whole year," Few said. "I'm just unbelievably proud of the group that we're down to."
The Gaels (10-4, 1-1) went 1-for-12 from beyond the arc and had just two assists. The only successful 3-pointer and both assists came late in the game. Saint Mary's came into Thursday action tied for second in NCAA Division I with 43.3 percent shooting on 3-pointers.
"We took a really good basketball team and guarded them great, kept them off the glass and scored on them," Few said.
The Bulldogs, tied for third in the nation prior to Thursday's games with 51.3 percent shooting from the floor, hit 49 percent overall and 47.4 percent on 3-pointers. The Zags were ranked seventh in 3-point shooting percentage at 42.6.
A 10-0 spurt pushed Gonzaga ahead 28-18 with five minutes left in the first half, and the Gaels never threatened the rest of the way. Gonzaga led 36-22 at the half, then quickly expanded the lead in the second half. The Gaels eventually fell behind by 30.
Senior forward Beau Levesque, the only Saint Mary's player to score in double figures, finished with 12 points. Junior forward Brad Waldow, who led the Gaels coming into the game with 16.8 points and 7.0 rebounds per game, went 1-for-8 from the field and totaled five points and three rebounds.
"We've been good at getting into the paint and kicking out, and we didn't do that tonight. We've got to get grittier and tougher. It starts with me and the senior leadership."
The Gaels have lost four of five after a 9-0 start. Gonzaga has won three in a row and nine of 10.
Eran Ganot, spending his second game as the Gaels' acting head coach, praised the Bulldogs at length and expressed great disappointment in his team's play. Ganot is filling in while Randy Bennett sits out the first five league games as part of NCAA sanctions against Saint Mary's for rules violations.
"That middle part of the game was inexcusable," Ganot said.
The Gaels had no answer for Karnowski at any time of the game. He helped defend Waldow and went 5-for-7 from the field and 5-for-6 at the free-throw line.
"He was just great," Few said. "He's been putting a lot of pressure on himself and making it harder than it is.
"We've been encouraging him, and I think we were looking for a breakout game like this."
"Angel gave us a really good effort off the bench," Karnowski said.
NOTES: The nationally televised game drew the standard sellout crowd of 6,000 at Gonzaga. ... Gonzaga and Saint Mary's join Duke and Kansas as the only Division I teams with 25 or more wins in each of the past six seasons. ... Gonzaga has won or shared 12 of the past 13 regular-season championships in the WCC. The Bulldogs finished second to Saint Mary's in 2011-12.