Mike Aaman and Romone Saunders scored 15 points each. Corey Henson added 10 points for the Seahawks, who handed the Huskies their first loss in a home opener on campus. UConn came in 27-0 in such games.
UConn trailed by three points at halftime and went more than 5 minutes without a basket to open the second half before Jalen Adams' tip-in made it 41-37.
Wagner scored the next eight, pushing the lead to 49-37 on a 3-pointer by Saunders.
But Saunders landed awkwardly making a pass under the basket a short time later and had to be helped to the bench.
He didn't return and UConn turned up the defensive pressure.
The Huskies went on a 12-0 run to tie the game, holding Wagner without a point for almost 7 minutes.
But Wagner responded, outscoring the Huskies 16-9 from there. Henson's 3-pointer with just over 3 minutes to play started a 7-0 run that put the game out of reach.
Wagner: The Seahawks head to Massachusetts for a game on Monday against UMass-Lowell. Their home opener comes Nov. 19 against Fairfield.
UConn: The Huskies have another home game Monday against Northeastern before heading west. The Huskies will play in coach Kevin Ollie's hometown of Los Angeles on Nov. 17 before heading to Hawaii and the Maui Jim Maui Invitational.