Islanders rookie Josh Bailey, who made his NHL debut on Tuesday, recorded his first point when he set up Okposo's second goal of the season 12:42 in, a power-play tally that tied it at 1.
Hunter gave New York a 2-1 lead with an unassisted effort on another man advantage 17:30 into the second. Guerin scored his sixth of the season early in the third.
Filip Kuba netted his first goal on a power play 1:53 in for Ottawa, which lost its third in a row after a 4-0-1 spurt.
MacDonald made his sixth straight start for the Islanders. He has started eight of nine games since No. 1 goalie Rick DiPietro was injured.
Ottawa's Alex Auld made 29 saves in his eighth start in nine games.
Islanders defenseman Thomas Pock was given a major penalty and a game misconduct 15:44 into the third period for elbowing Ottawa's Ryan Shannon. Shannon, who made his Senators debut, had to be helped off the ice to the dressing room.
New York's Richard Park was called for slashing with 45.2 seconds remaining but Ottawa, which had pulled Auld, was unable to score with a 6-on-3 skating advantage.
Senators forward Jarko Ruutu began serving a two-game NHL suspension for elbowing Montreal's Maxim Lapierre in the head Tuesday in Ottawa's 4-0 road loss. Ruutu will also sit out Saturday against the Islanders on Long Island.
New York held a 16-5 shots advantage in the first, including four before Islanders forward Sean Bergenheim was called for hooking at 1:09.
Ottawa took advantage on the power play when Kuba scored his first goal in 16 games on the Senators' first shot. Kuba, who leads the Senators with 14 assists, one-timed Jason Spezza's pass from the left side, driving a slap shot past Joey MacDonald from the high slot 1:53 in.
Bailey, who debuted Tuesday during the Islanders' 3-1 home loss to Philadelphia, made a fine pass on the tying goal. Okposo received the puck in the slot and fired it into a wide open left side.
Hunter put the Islanders ahead 2-1 when he backhanded a loose puck in the crease past Auld after Kuba was unable to clear it following a faceoff.
Guerin scored 2:31 into the third, finishing off Doug Weight's pass across the crease from the right edge.
Notes: The 19-year-old Bailey was chosen ninth overall by the Islanders in this year's draft, held at Scotiabank Place - the Senators' home arena. ... Shannon, recalled from Binghamton of the AHL on Wednesday, played with Spezza and Dany Heatley on the Senators' top line.
