The loss dropped Anaheim to 12-26-4 on the season and 8-12-1 on home ice. The Ducks now sit 3-5-1 on the homestand, heading to Friday's finale vs. New Jersey.
Sam Carrick and Simon Benoit scored for Anaheim. Max Comtois added two assists. Making his 28th start of the season John Gibson made 31 saves in two periods of action. Anthony Stolarz stopped all 16 shots he faced in the third.
Dylan Holloway, Ryan Nugent-Hopkins, Connor McDavid, Klim Kostin (twice) and Leon Draisaitl scored for the Oilers, who avoided a three-game losing skid and improved to 22-18-3 on the year.
First-year Oiler netminder Jack Campbell earned his 10th win in the orange, blue and white with 21 saves.
A day after Anaheim's head coach, Dallas Eakins, pointed to clean breakouts as a key to the club's success against Edmonton, the Ducks surrendered four first-period goals, each directly following defensive zone turnovers.
The first came on the type of goal that has established McDavid as one of the game's greats. After the Ducks turned the puck over in the defensive zone, the Oiler captain took a pass behind the Anaheim net, keeping his back to the slot before delivering a perfect backhand pass to Holloway, who swiped it home before Gibson could adjust.
McDavid has points in 23 of his last 24 games, including his last five appearances. With two points on the night, the 25-year-old, who ranks fourth in NHL history in career points-per-game, owns 36 points in 22 career matchups against Anaheim.
Holloway has goals in two of his last four games, his second and third career NHL markers.
Nugent-Hopkins doubled the lead 74 seconds later on a fortunate bounce for the visitors. After the Ducks failed to evacuate their defensive zone following a won faceoff, Edmonton got the puck to Nugent-Hopkins at the right point, where he stepped in and fired a wrister off Fowler's foot, changing the shot's course just enough to fool Gibson and give the Oilers a 2-0 edge.
The goal clinched Nugent-Hopkins' fifth career twenty-goal season and his first since the 2019-20 campaign. The first overall pick in 2011 and now the longest-tenured active Oiler, Nugent-Hopkins became the club's fourth 20-goal scorer this season (also McDavid, Leon Draisaitl and Zach Hyman), the most by any NHL club through 43 games since 1995-96.
Anaheim temporarily got back within a goal on a hard-working shift by the third line. As Carrick and Comtois went to work on the forecheck behind the net, Carrick poked a loose puck free behind the cage for his linemmate. Comtois then hustled around the net with a defender on his back and returned to the favor to Carrick, delivering a backdoor pass that the centerman buried through Campbell to cut the host's deficit in half.