Cameron Wright added 11 points for the ninth-seeded Panthers (26-9), who will likely face top-seeded Florida in round three of the South Region. The Gators take on 16th-seeded Albany later on Thursday. A top seed has never lost in its opening game in tournament history.
Lamar Patterson ended with 10 points as Pittsburgh dominated from the opening tip. The Panthers scored the first 13 points of the game, led by 20 just over 12 minutes into the contest and scored 46 first-half points.
Josh Scott scored 14 points and Xavier Johnson had 11 points for eighth-seeded Colorado (23-12), which never got going offensively despite being the higher seeded team.
Behind Zanna, Pitt scored the first 13 points of the game and never looked back. Zanna scored eight of his 16 first-half points during the opening surge and the rout was on.
The lead later reached 20 points when Josh Newkirk's layup with 7:44 left in the first half gave the Panthers a 28-7 lead. Then, with 1:55 remaining in the half, Zanna's two free throws extended the cushion to 28 points, 44-16.
After continuing to hold a 28-point cushion at halftime, 46-18, the lead reached 30 points for the first time when Michael Young opened the stanza's scoring with a layup 27 seconds in.
Colorado could only manage to draw within 28 points from there.