In the five games before his hot streak, Karlsson had a single goal.
His two assists Sunday gave him 65 points and the record for most points in a season by a Senators' defenseman.
"I'm obviously happy about it but it's not something that is going to be in my mind for long right now. I'm going to have to wait until after the season to think about it," Karlsson said of the record.
"We've scored a lot of goals here over the last couple of games and obviously that helps out a lot."
The Senators led 2-1 heading into the third period when a turnover by Islanders defenseman Mike Mottau led directly to Ottawa's third goal.
Mottau tried to backhand a pass from behind his net up the middle, but it went first to Neil and then O'Brien, who took a wrist shot that caught the top of Nabokov's glove before going in.
After Parenteau pulled the Islanders to within a goal at 9:04, Neil tapped Nick Foligno's pass out of midair and past Nabokov at 12:59 to restore the Senators' two-goal lead. Turris scored into an empty net to seal the victory.
"It was a big win all around," Spezza said. "It was a hard fought game and Robin did a good job of keeping us in that first period. It wasn't the best first 10 minutes we've had and he kept it 1-0 and gave us a chance to hang around in the game."
The Senators converted both their power-play opportunities in the second period to take a 2-1 lead.
Karlsson fed Michalek in the slot and he then put a backhand past Nabokov at 12:21 to tie the game.
Just over four minutes later, Spezza ripped a slap shot over Nabokov's shoulder and in from the top of the faceoff circle. Karlsson had set up the play by faking a shot, then feeding Spezza cross ice.
"We've got to take a little more pride in our game and get back to our foundation, where it was at the start of the year. Some of the guys should look in the mirror and know they could have worked a little harder tonight and been a little stronger on the puck at times," Islanders coach Jack Capuano said.
"You can't look back though and you have to look forward. This next week is going to be huge."
The Islanders had taken a 1-0 lead just 49 seconds into the game as Tavares beat Lehner finishing up a two-on-one for his 25th goal.
Prior to Sunday's game the Senators made a trade acquiring goaltender Ben Bishop from the St. Louis Blues in exchange for their second-round pick in the 2013 NHL draft. Bishop had spent the entire season with the Peoria Rivermen of the American Hockey league and has a 24-24-0 record. ... Brian Rolston, Steve Staios and Josh Bailey were scratches for the Islanders Sunday while Zenon Konopka and Matt Carkner sat for the Senators..