Dean McAmmond and Dany Heatley also scored for Ottawa, which is fighting for fourth place in the Eastern Conference. Martin Gerber stopped 21 shots to win his 15th game this season.
Viktor Kozlov and Marc-Andre Bergeron scored for the Islanders, who started the night in 10th place in the East. They have only four games left to make up a four-point gap and get into the playoffs. Alexei Yashin had a pair of assists for New York, winless in four games (0-3-1).
Wade Dubielewicz made his first start of the season for New York and turned aside 42 shots. He filled in for Mike Dunham, who started the previous two games in place of injured regular Rick DiPietro.
Dubielewicz made a fine right pad kick save at the left post on Joseph Corvo at 9:24 of the first period, but was matched by Gerber's left-arm stop on Viktor Kozlov's breakaway attempt with 1:34 left.
The Senators took the lead with 19.9 seconds remaining in the opening frame when Jason Spezza started a 2-on-1 break with Islanders defenceman Marc-Andre Bergeron trapped in Ottawa's zone. Spezza rushed down right wing and threw a perfectly timed pass across to Schubert, who found the open left side.
The Islanders tied it when Kozlov slammed in a pass from Yashin for his career high 25th goal at 11:11.
Ottawa regained the lead 28 seconds later when Comrie burned newly acquired defenceman Deron Quint on a move, and beat Dubielewicz on a short shot.
Quint was signed by the Islanders on Friday, as injuries to regulars Radek Martinek, Bruno Gervais and Freddy Meyer left the team short on the blue-line.
Comrie finished off the Islanders with his second goal of the game just 47 seconds into the final period.
Just as an Ottawa penalty expired, McAmmond took a back pass from Daniel Alfredsson and put a wrist shot between Dubielewicz's pads at 4:47 to make it 4-1.
Heatley wrapped up the scoring with an empty-net goal, his 48th of the season, with 1:40 left.
Notes: D Todd Simpson, signed by the Islanders on Thursday, didn't play because the NHL honoured a suspension he incurred while playing for in the German league. Simpson was suspended indefinitely for abuse of an official, pending a hearing Monday. ... The Islanders have allowed at least one goal in 15 of the 17 full periods they've played without DiPietro since he sustained a concussion at Montreal on March 13. ... The Islanders have won just twice in 17 home meetings with the Senators. They won both home games in the 2003-04 season. Ottawa has won eight straight overall against New York, dating to a 5-2 Islanders win at home on Jan. 19, 2004.