Kyle Okposo, Trent Hunter and Bill Guerin each lit the lamp for the Islanders, who snapped a three-game skid.
"We've blown leads in four out of the last six games and two of them were two-goal leads in the third," said New York's Doug Weight. "Certainly it was a challenge for us tonight. Today we played better in the third and we skated better."
Filip Kuba scored the lone goal for the Senators, losers in three straight, while Alex Auld was charged with all three goals on 31 shots in the loss.
"We started the game with no level of competitiveness," said Ottawa coach Craig Hartsburg. "You can't allow that or you won't win many games. I don't know if you would call it a wake-up call, but we need to wake up."
These teams will meet on Saturday at New York.
The Senators opened the scoring in the game with a power-play goal as Jason Spezza fired a pass from the low left circle to the slot where Kuba one-timed it past MacDonald just 1:53 into the game.
The Islanders, though, answered with a power-play goal of their own to tie the game. After a blast from the right point went wide, Josh Bailey grabbed the puck at the low right circle and his quick pass to Okposo was one-timed past Auld with 7:18 left in the first.
Late in the second period while skating on the man advantage, New York took the lead. A right circle faceoff resulted in the puck going back and bouncing off the backboards. It then kicked out to the front of the net where Hunter backhanded it in with 2:30 left in the second.
The Islanders tacked on an insurance goal just 2:31 into the third. Weight had the puck and skated to the low left side to get Auld out of position. From a sharp angle, Weight threw the puck to the other side of the net where Guerin slammed it home for a 3-1 advantage.
"Being in the crease is pretty much my range," said Guerin. "I have to go there for it to go in most nights."
MacDonald shined in the third period as he made several big saves and finished the frame with 16 stops to preserve the win.