The loss drops the 'Dogs' record to 22-15-1-1.
Rochester (24-11-1-0) opened the scoring 6:30 into the first period on a power-play goal by Drew Larman, giving the Americans a 1-0 lead.
Drew Stafford made it 2-0 at 4:30 into the second period, beating 'Dogs goaltender Yann Danis.
Hamilton made it a one-goal game 6:27 into the second when Zack Stortini poked in a rebound to make it 2-1. Jean-Philippe Cote earned an assist on Stortini's ninth goal of the season.
Rochester regained its two-goal lead at 10:39 of the second period when Larman used a Hamilton defenceman as a screen, firing a shot over Danis' shoulder to make it 3-1.
The Americans sealed the win with an empty netter by Daniel Paille with 52 seconds left in the third.
Danis stopped 26 of 29 shots to suffer the loss, while Craig Anderson made 32 saves on 33 shots to earn the win for the Amerks.