Booker's game-winner gave him 15 points for the Buffaloes (9-1), who bested Kansas for the first time since Jan. 22, 2003, when Colorado was a member of the Big 12 Conference.
Spencer Dinwiddie complemented Booker with a 15-point, seven-assist effort.
Xavier Johnson and Josh Scott chipped in 14 points each for the Buffaloes.
Freshman Andrew Wiggins scored 22 points for the Jayhawks (6-2), who fell in their first true road game this season.
Kansas committed 14 turnovers in its second defeat in three games.