'Coach K' is in his 42nd season in charge at the school, and is searching for his sixth national championship.
His Blue Devils took on Michigan State and fellow Naismith Memorial Basketball Hall of Fame coach Tom Izzo in the second round on Sunday, pulling away late to win 85-76.
Duke boasts three likely first round picks in this year's NBA Draft, and they showed exactly why, headlined by potential number one overall Paolo Banchero.
Banchero, who stands at six-foot-10, showed his all-round game, hitting tough pull-up jump shots, flashing an advanced interior passing game and defensive mobility to finish with a team-high 19 points on 8-of-14 shooting, including 2-of-5 from long range, and an equal team-high four assists.
A record-breaking sixth NCAA Tournament encounter between the pair was secured after both Duke and Michigan State won their first-round matchups on Friday – Krzyzewski's second seed beating Cal State Fullerton 78-61 while Izzo's number seven outfit scraped past Davidson 74-73.
It is fitting that the final March Madness of Krzyzewski's 42-year Duke career should see him again take on Izzo, with their sixth coaching clash passing the previous benchmark of five.
Until now, that record was held jointly with two other coaching duos: Roy Williams and Bill Self, and Eddie Sutton and Denny Crum.
'Coach K' and the Blue Devils are 12-3 against Izzo's Spartans and 3-2 in the NCAA Tournament, with Duke's most recent March Madness victory in the series coming en route to the 2015 championship.
However, another win for Izzo – himself 27 years in at Michigan State – would conclude both Krzyzewski's bid for a sixth national title and his career, stopping him just short of 100 NCAA Tournament wins; his 98 as of Friday are already a record.
Either way, Izzo is delighted just to get the chance to test himself against one of basketball's greatest names one last time.
"I like the game, I just don't like the record in that matchup over the years," Izzo said. "I've got to be his favourite coach because he's beaten us like a drum.
"I didn't want to look ahead and dream of the matchup, because you get a chance, one more time, to play against maybe the all-time great, as they say about LeBron [James] or they say about Michael [Jordan].
"In the coaching world, the 'GOAT' is the team we'll play, and it's been earned. It's not been given. It's been earned.
"And you know, I'm going to try my hardest to see if we can get one more on the positive side of that thing, but every time we've played it's been a game I looked forward to."
Timme, a senior, was named a consensus First-Team All-American this year after back-to-back Second-Team selections in his sophomore and junior seasons.
While his career at Gonzaga has been littered with individual honours, the six-foot-10 fringe NBA prospect looked destined to end his run as a Bulldog without capturing their elusive first National Championship as they trailed 46-33 at half-time.
But Timme would not let three-seed Gonzaga go down quietly, putting together a monstrous 36 points on 16-of-24 shooting while adding 13 rebounds, four assists and two blocks to turn their deficit into a 72-62 lead with 2:30 remaining.
UCLA's Jaime Jaquez Jr made things interesting with a quick eight-point burst on his way to a team-high 29 (12-of-25 shooting), 11 rebounds, three assists and three steals, setting up Amari Bailey for a three-pointer to put the Bruins back in front 76-75 with 13 seconds on the clock.
With the game on the line, Julian Strawther drained the clutch three to give Gonzaga the lead and the win, booking their fifth Elite 8 trip from the past eight editions of the tournament.
Gonzaga will face the four-seed Connecticut Huskies next after they wiped the floor with the eight-seed Arkansas Razorbacks 88-65.
It was another strong performance from UConn's top NBA prospect Jordan Hawkins, as the lanky six-foot-five wing dropped a game-high 24 points on six-of-13 shooting with three assists, marking the third tournament game in a row he has drained at least three three-pointers.
The nine-seed Florida Atlantic Owls are through to their first Elite 8 in school history after upsetting the four-seed Tennessee Volunteers 62-55.
The Owls came into the tournament at 31-3, and while there were questions about their strength of schedule, they have continued to prove they are one of college basketball's best teams this year, holding Tennessee to just 33 per cent shooting.
Florida Atlantic will play Kansas State in the next stage after the Wildcats survived a thrilling 98-93 overtime battle against Tom Izzo's Michigan State Spartans.
Five-foot-eight Wildcats point guard Markquis Nowell played the game of his life, ending up with 20 points (seven-of-18 shooting), 19 assists, five steals and just two turnovers in his 43 minutes.
He joins Chris Paul and James Harden as the only players from either division one college basketball or the NBA in the past decade to put up a game of at least 20 points, 15 assists and five steals.
The Spartans rode a 23-point performance from senior point guard Tyson Walker, while Joey Hauser – brother of Boston Celtics wing Sam Hauser – collected 14 points and 10 rebounds.
As well as pulling into a tie for the sixth-most Sweet 16 appearances in head coaching history, Izzo also claimed the record for the most ever NCAA Tournament wins as the lower seed, with this his 16th.
He is one more Sweet 16 trip away from tying Louisville legend Denny Crum for the fifth-most, with only North Carolina's Roy Williams (19), Syracuse's Jim Boeheim (20), Michael Jordan's North Carolina coach Dean Smith (21) and Duke's Mike Krzyzewski (26) having more.
The seven-seed Spartans will next face three-seed Kansas State after they won the battle of the Wildcats 75-69 against six-seed Kentucky.
Reigning National Player of the Year Oscar Tshiebwe was monstrous with 25 points and 18 rebounds, while projected first-round draft pick Cason Wallace impressed with 21 points (nine-of-11 shooting), nine rebounds, four assists and two steals.
But their performances were not enough to lift Kentucky to the victory, as diminutive five-foot-eight point guard Markquis Nowell dropped a game-high 27 points and nine assists to carry Kansas State through.
Following his massive 28-point, 13-rebound showing in his side's opening-round win, Connecticut Huskies center Adama Sonogo starred again with 24 points (11-of-16 shooting) and eight rebounds in a 70-55 win over the Saint Mary's Gaels.
After Marquette, the top seed to fall Sunday was the three-seed Baylor Bears. Despite 30 points from Baylor guard L.J. Cryer, the Creighton Bluejays received a game-winning 30 points from Ryan Nembhard in the 85-76 triumph.
Nembhard is the younger brother of Andrew, who has been a rookie standout for the Indiana Pacers this season.
Following their stunning upset of one-seed Purdue, where they became the second 16-seed to ever advance past the first round, the Fairleigh Dickinson Knights were sent packing 78-70 by the nine-seed Florida Atlantic Owls.
Three-seed Xavier were in control throughout their 84-73 win against Pittsburgh, five-seed Miami prevailed 85-69 over four-seed Indiana, and four-seed Gonzaga sent six-seed TCU home 84-81.
