It began on March 14, 2006, and concluded with the championship game on April 3 at the RCA Dome in Indianapolis, Indiana.

For only the second time in history, an 11-seed advanced to the Final Four as George Mason of the Colonial Athletic Association (CAA) won the Washington, D.C. region.

Florida won its first-ever national basketball championship by defeating UCLA 73–57 in the final game.

Penn earned an automatic bid by winning the regular-season title of the Ivy League, which did not conduct a conference tournament.

The remaining 34 teams were granted "at-large" bids, which are extended by the NCAA Selection Committee.

[1] The following are the sites that were selected to host each round of the 2006 tournament: Opening Round First and Second Rounds Regional semifinals and finals (Sweet Sixteen and Elite Eight) National semifinals and championship (Final Four and championship) The following teams were automatic qualifiers for the 2006 NCAA field by virtue of winning their conference's tournament (except for the Ivy League, whose regular-season champion received the automatic bid).

The columns R32, S16, E8, F4, and CG respectively stand for the Round of 32, Sweet Sixteen, Elite Eight, Final Four, and championship Game.

Greg Gumbel once again served as the studio host, joined by analysts Clark Kellogg and Seth Davis.