The Final Four consisted of Kentucky, making their second appearance in the Final Four under John Calipari, Louisville, making their second appearance under Rick Pitino and first since 2005, Kansas, making their first appearance since winning the 2008 national championship under head coach Bill Self by defeating Calipari's Memphis team, and Ohio State, making their first appearance since their runner-up finish in 2007 and second under coach Thad Matta.

Kentucky defeated Kansas 67-59 to win their first national championship since Tubby Smith led the team there in 1998. This was Calipari's first national championship in four trips to the Final Four, having previously gone there with Kentucky in 2011, Memphis in 2008 and Massachusetts in 1996.

Upsets were once again the story of the tournament in 2012, and for the first time ever two #15 seeds won in the same tournament. In the South Region, #15 Lehigh of the Patriot League defeated #2 Duke. In the West Region, #15 Norfolk State of the MEAC, making their first ever NCAA tournament appearance, defeated #2 Missouri. In addition to this, Ohio won a game as a double digit seed for the second time in four tournaments as the #13 seed Bobcats defeated #4 seed Michigan to advance to the third round of the Midwest Region. A team from the First Four games also won in the Round of 64 for the second consecutive year as South Florida defeated Midwest #5 seed Temple, setting up a #12 vs. #13 matchup that Ohio won.

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