This tournament is the first to feature 65 teams, due to the Mountain West Conference receiving an automatic bid for the first time. This meant that 31 conferences would have automatic bids to the tournament. The NCAA decided to maintain 34 at-large bids, which necessitated a play-in game between the #64 and #65 ranked teams, with the winner playing against a #1 seed in the first round. (Another option would have been to reduce the number of at-large bids to 33, which was the option chosen for the women's tournament.) This is also the first tournament to have been broadcast in high-definition, being broadcast on CBS.
This was the last tournament where the first- and second-round sites were tied to specific regionals. The "pod system" was instituted for the 2002 tournament to keep as many teams as possible closer to their campus in the first two rounds.
The Final Four consisted of Duke, making their second appearance in the Final Four in three years, Maryland, making their first appearance, Michigan State, the defending national champions, and Arizona, making their first appearance since winning the national championship in 1997.
Duke defeated Arizona 82-72 in the national championship game to win their third national title and first since 1992. Shane Battier of Duke was named the tournament's Most Outstanding Player.
For the second time, the Metrodome in Minneapolis hosted the Final Four; it was its last time hosting the event, as the building has been replaced by U.S. Bank Stadium, which will host the Final Four in 2019. The Metrodome was the last of four MLB stadiums to host Final Fours, including the Astrodome, the Kingdome and Tropicana Field. Three of the four regional cities were former Final Four host cities; Anaheim is within the Los Angeles metropolitan area but has not hosted itself. There were two new venues in cities that had previously hosted tournament games. The First Union Center (now Wells Fargo Center) hosted games for the first time, replacing its neighbor, The Spectrum. Cox Arena, located within the shell of the old Aztec Bowl at San Diego State University, was also a new venue, hosting games in San Diego for the first time since the 1975 Final Four. This also marked the second straight year that a new on-campus venue was used for the tournament. The 2001 tournament marked the last time hosting for Nassau Coliseum and the Memphis Pyramid. The Pyramid has since been converted into a Bass Pro Shops destination store, and the Nassau Coliseum was recently renovated into a smaller arena, lessening the chances that it will return to the tournament. Any future tournament games to be held in Long Island or Memphis would be played at Barclays Center or FedEx Forum, respectively.
The fourth meeting of the year between ACC teams Duke and Maryland turned into a classic. Maryland jumped out of the gate to an early 39-17 lead. It appeared the Terps would eliminate Duke, led by senior Shane Battier. However, Duke was able to cut the lead at halftime to 49-38. Duke would take its first lead when Jason Williams drained a three to give Duke the lead 73-72 with 6:48 to play. Duke closed the game with a 23–12 run to stun Gary Williams' Maryland squad. Referees: David Libbey, Mark Reischling, and Ted Hillary.
In an emotional season in which coach Lute Olson suffered the loss of his wife, he would be just 40 minutes away from a second National Championship after his Wildcats destroyed the defending national champion Michigan State Spartans. The game was close at halftime with Arizona leading by just 2. However, Arizona outscored Michigan State 48–31 in the second half en route to the 19-point victory.
The second-ranked team coming into the NCAA Tournament would leave giving coach Mike Krzyzewski his third National Championship at Duke. Arizona cut Duke's lead to 39-37 early in the second half, but Mike Dunleavy Jr. connected on three three-pointers during an 11–2 Duke run. Dunleavy Jr. led the Duke Blue Devils with 21 points. The Arizona Wildcats would cut the gap to 3 four times, twice inside the four-minute TV timeout. However, Shane Battier proved himself too much for the Wildcats to handle as he hit two critical shots to put the Blue Devils comfortably ahead. Jason Williams, despite a poor shooting night, iced the game with a three-pointer from the top of the key with under 2 minutes to play to give Duke a three-point lead. The final score was Duke 82 – Arizona 72.
This tournament featured many upsets in the first two rounds, with two #13 seeds and two #12 seeds winning in the first. The best remembered and most unexpected occurred when Hampton beat number 2 seed Iowa State 58-57 in the first round. The Pirates were down by as much as 11 in the game and outscored the Cyclones 10-0 in the final seven minutes of the game. Tarvis Williams made the winning shot with 6.9 seconds left. The video of Hampton coach Steve Merfield being lifted in the air by player David Johnson during the celebration has become a classic clip, often played by CBS and ESPN to showcase the excitement of the underdog in the NCAA Tournament.
Hampton became only the fourth #15 seed to win a game since the tournament expanded to 64 teams in 1985 and the first since 1997. They went on to lose to Georgetown in the second round, failing to become the first seed that low to make the Round of 16. The Pirates were the last #15 seed to advance in the tournament until 2012, in which two #15 seeds beat their #2-seeded opponents.
12 seeded Gonzaga also made the Sweet 16 for the third year in a row, all as a double digit seed.