The 7-foot-1 Kalkbrenner did a little bit of everything for the Bluejays, which included hitting a big 3-pointer on a day the team finished 3 of 20 from long range.
The slender Kalkbrenner had six dunks and 10 rebounds, and North Carolina State big men D.J. Burns Jr. and Ebenezer Dowuona were hampered by foul trouble.
"Nothing surprises me from Kalk," Creighton coach Greg McDermott said. "He's just improved in every facet of the game, and he was able to score on Burns. But then when they had to go small, we did a good job of executing some offense to get him the ball around the rim, and then he did the rest."
Next up for the Bluejays (22-12) is third-seeded Baylor in the second round in the South Region. The Bears beat Santa Barbara in the early game.
Leading 62-59, Baylor Scheierman drained a 3-pointer with 2:23 remaining to give Creighton some separation. A pair of free throws for Kalkbrenner, a block by Trey Alexander and another basket from Scheierman - complete with blowing the crowd a kiss - and the Bluejays were on their way to a hard-earned win.
About that kiss: "It was just an in-the-moment thing," Scheierman explained. "It wasn't necessarily to anybody."
Terquavion Smith led the Wolfpack (23-11) with 32 points. The team started slowly, going 0 for 8 from the field to open the game, and never found its rhythm from deep. It was 3 for 14 from 3-point range.
"We knew their game plan. We knew what they were going to do," said Wolfpack guard Jarkel Joiner, whose team led by seven with 16:48 remaining. "We could've been more disruptive because they're a great passing team. But give credit to them - they found their big man."
Still, it's been quite a turnaround for a North Carolina State team that went 11-21 last season.
"We are going to walk out of here with our head up," N.C. State coach Kevin Keatts said. "Continue to build and keep pushing this program in the right direction."
Pregame Coverage:
NC State fans gather in Denver to cheer on Wolfpack
AP March Madness coverage: https://apnews.com/hub/march-madness and bracket: https://apnews.com/hub/ncaa-mens-bracket and https://apnews.com/hub/ap-top-25-college-basketball-poll and https://twitter.com/AP_Top2
NCAA tournament scores from ESPN
What to know about every team in the men's NCAA tournament bracket
The Associated Press contributed.