Alexei Yashin scored the tying goal with 3:43 left in regulation for the Islanders, who had opened the season with three straight losses for the first time in the franchise's 35-year history. They won despite getting outshot 50-24.
Samuel Pahlsson scored his first two goals of the season, Corey Perry also scored and Chris Pronger had a goal and an assist for the Ducks, who had their first 3-0 start since the NHL expanded to Anaheim for the 1993-94 season.
Ten-year veteran Mike Dunham made his first start in goal for the Islanders, making 46 saves. Rick DiPietro, who signed a 15-year,US$67.5 million contract last month, took the loss in New York's first three games.
The 34-year-old Dunham won the backup job in training camp as a non-roster invitee after spending last season with Atlanta.
The Ducks made quick work of the Islanders' penalty-killing unit twice in the third period. Pronger converted Chris Kunitz's pass from behind the net just five seconds after Brendan Witt was penalized for cross-checking. Perry connected on a rebound at the edge of the crease just six seconds after Sean Hill was sent off for tripping.
Jean-Sebastien Giguere, playing in his 300th regular-season game and coming off a shutout of St. Louis on Monday night, surrendered three goals on four shots as the Islanders grabbed a 3-1 lead at 5:28 of the second.
York converted Arron Asham's pass form behind the net, beating Giguere to the stick side after a turnover deep in the Anaheim zone. The Islanders pulled ahead 43 seconds later when Hunter threw a lazy wrist shot at the net through a screen from the right point and the puck got through a maze of players before eluding Giguere's glove.
Simon gave the Islanders a two-goal lead 63 seconds later on a power play.
Notes: Dunham is the sixth player to have played for the Islanders, Rangers and Devils, and the second goaltender to do it - along with John Vanbiesbrouck. ... The victory was the first for Islanders coach Ted Nolan in the NHL since the 1996-97 campaign, when he was named coach of the year in just his second season in the league.