The 2010 NCAA Division I Women's Basketball Tournament started Saturday, March 20, 2010 and was completed on Tuesday, April 6 of the same year with University of Connecticut Huskies defending their title from the previous year by defeating Stanford, 53-47.

The top seeded Tennessee Lady Vols faced the Baylor Lady Bears in the Memphis Regional semifinals. This was a rematch of the season open for the two teams, a game won by Tennessee 74–65. Earlier in March, the freshman center for Baylor, Brittney Griner had broken the nose of Jordan Barncastle in a game against Texas Tech, which resulted in Griner playing more tentative, concerned about drawing attention to the referees. She was not tentative in the game against the Lady Vols, scoring 27 points and recording ten blocks. Despite her performance, Tennessee led by five points with under eight minutes to go in the game. Baylor then went on a 21–1 run to take a 15-point lead, and command of the game. Baylor won 77–62 to advance to the regional finals.

Stanford more than doubled up Georgia, winning 73–36 in the regional semifinal, then faced Xavier. Although Stanford opened up an early five-point lead, Xavier cut the lead to one. The Cardinal extended the lead to five again, and the Musketeers cut the lead to two points at the half. Stanford opened up a six-point lead in the second half, but Xavier responded to take a lead. With just under a minute to go, Xavier took a two-point lead and Kayla Pedersen hit a jumper to tie the game at 53 points apiece. With 18 seconds left, Xavier ran a play that opened up Delaquese Jernigan under the basket. She received the ball, and missed a point-blank uncontested layup. The rebound came out beyond the three-point line to Amber Harris. The Cardinal were trying to cover the Xavier players, but missed Jernigan standing by herself under the basket. Harris passed the ball in to Jernigan who took an uncontested layup and missed it again. With only four seconds left in the game Jeanette Pohlen drove the length of the court, weaving among defenders, and threw up a shot with under a second left. The shot went in and the Cardinal won 55–53 to advance.

In the Kansas City Regional, both top seeds were upset in the semifinal round. Kentucky, led by 21 point from A'dia Mathies, opened up a lead ant he second half, extended it to 19 points, and were victorious, beating Nebraska 76–67 to advance to the regional finals. The regional semifinal game was a second of the season for Oklahoma and Notre Dame, a game the Irish has won in the regular season. In this game the score was tied early, while Oklahoma took a slim lead at the half. They extended the lead to eight points in the second half, but Notre Dame took the lead back at 50–49. With less than a minute to play, Oklahoma took a three-point lead, but Skyler Diggins hit a three-pointer to tie the game at 66 points each. Oklahoma had the ball for the last possession, but never got a shot off, so the game went to overtime. The game was tied with 72 points for each team with seconds to go when Oklahoma had another chance. This time, Nyeshia Stevenson hit a three-pointer, giving the Sooners a three-point lead with just over four seconds to go. Notre Dame tried a long inbounds pass, but were unsuccessful, and Oklahoma won 77–72.

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