Guerin scored the decisive goal early in the third period, MacDonald made 35 saves, and the Islanders sent the reeling Buffalo Sabres to their fifth straight loss, 4-2 on Saturday night.
MacDonald turned aside 30 shots over the first two periods, including 18 in the second to keep the Islanders' one-goal lead intact. New York recorded only two shots in the period but outscored the Sabres 1-0.
Guerin then capitalized four minutes into the third when he scored his seventh goal to push New York's lead to 3-1.
"We needed a bit of a cushion," Guerin said. "When you're up against a talented team like Buffalo you know they can turn it up at any given moment and produce offense. The bigger the cushion, the better."
MacDonald was steady in his 10th straight start since taking over for the injured Rick DiPietro, and avenged an earlier loss this season to the Sabres in which he allowed seven goals. He also rebounded after allowing five goals in a 5-2 loss to the New Jersey Devils on Friday night.
"That's what my job is. I have to come up and make the save when we need it," he said. "They threw a lot of pucks on the net in the second period, but our defense also did a great job clearing the rebounds and giving them only one opportunity."
"When we're in the lead, we feel we deserve it and aren't completely shocked," Guerin said. "It has a lot to do with us being comfortable in that position."
After starting 8-2-2, the Sabres are in the midst of a 1-6-1 slide.
"I'd rather take the goal back and win the game," Mancari said. "That's what's important right now."
It was the second straight game that Buffalo was stymied by a goalie on top of his game. Martin Biron made 40 saves Friday night in Philadelphia's 3-0 win over the Sabres.
"We had no emotion early on," Buffalo forward Jason Pominville said. "We weren't competing and we lost a lot of one-on-one battles."
Roy made it 3-2 when he beat MacDonald with a slap shot from the top of the left circle with 4:34 to go, but Streit capped New York's win with an empty-net, power-play goal with 2 seconds left.
Hilbert opened the scoring 14 minutes in with his fifth goal. Trent Hunter's shot from the slot ricocheted off Hilbert before bouncing over Lalime to make it 1-0.
Mancari tied it with 1:01 left in the opening period. After MacDonald stopped Paul Gaustad's shot from the left circle, Mancari shoveled in the rebound.
Buffalo had allowed nine consecutive goals over three games before the tally.
The Islanders regained their one-goal edge on Sim's fifth goal at 7:41 of the second period. On the power play, Streit's slap shot from the right point went off Sim and past Lalime to give New York a 2-1 advantage.
"We didn't do enough good things," Sabres coach Lindy Ruff said. "We're in tough right now."
The Sabres played the second of a season-high, four-game homestand. ... The Islanders recalled C Jeremy Colliton from Bridgeport of the AHL. Colliton replaced Frans Nielsen, who sustained head and leg injuries Friday when elbowed by Devils defenseman Mike Mottau. Nielsen is expected to miss eight to 12 weeks due to multiple injuries to his right leg. He didn't suffer a concussion. Mottau received a two-game suspension from the NHL. ... Hunter notched his 100th career NHL assist on Hilbert's goal. ... Buffalo scratched D Henrik Tallinder and RW Maxim Afinogenov for the second straight game. ... The Islanders snapped a three-game losing streak to the Sabres.