Frattin skated in from the left circle and wristed a shot over the shoulder of Sabres goalie Ryan Miller.
Jay McClement and Cody Franson also scored for Toronto, which snapped a two-game skid. James Reimer made 29 saves for the Maple Leafs.
Jason Pominville, Andrej Sekera and Mikhail Grigorenko scored for Buffalo, which lost its fourth straight. Miller stopped 20 shots.
Grigorenko, the Sabres' first-round choice in the 2012 draft, tied it 3-all at 7:10 of the third period with a deftly placed backhander from the slot. He made amends for being on the ice for the first three Toronto goals.