The Islanders started Al Montoya between the pipes, and a Matt Moulson goal just 43 seconds into the third period had them on top 3-2 and in the lead for the first time on the evening.
But Tom Pyatt and Tim Wallace each slammed home a goal roughly three minutes apart to give Tampa Bay the 4-3 lead and ultimately the win.
Moulson's goal was his 33rd on the season, while both Frans Nielsen and Kyle Okposo also added tallies for New York.
The loss keeps the Isles at 71 points, tied with Montreal for last in the Eastern Conference. They'll skate again on Sunday afternoon when they travel to Florida to take on the Panthers.
For more on the Islanders, head over to the SB Nation blog Lighthouse Hockey.