Connor McDavid added a goal and two assists for Edmonton, which earned its third straight win. Darnell Nurse had a goal and an assist, and Jujhar Khaira and James Neal also scored. Tyson Barrie had three assists.
Draisaitl's third career hat trick helped the Oilers improve to 6-0-0 against the Senators this season. The teams finish their three-game series on Friday night.
''Connor and Leon are both world-class players, and quite a bit different,'' Barrie said. ''They go about it in different games. Leon, the way he thinks the game and the way he passes the puck on his forehand, backhand ... he slows the game down, but finds guys with speed. It's pretty incredible.
''Really grateful to get out there with those two on a nightly basis.''
Edmonton's win streak comes after it dropped three in a row to Toronto by a combined 13-1 score. Draisaitl, who has 15 points against Ottawa this season, said it was up to himself and McDavid to lead the Oilers' resurgence.
''That's our job as go-to guys,'' he said. ''It's our job as a leadership group and collectively as a team to find our way out of it.
''Huge props to our group.''
Matt Murray stopped 29 shots for Ottawa, and Evgenii Dadonov spoiled Mike Smith's shutout bid midway through the third period. Ottawa's D.J. Smith had a forgettable night in his 100th game as an NHL head coach.
''Everyone hates losing,'' Senators winger Brady Tkachuk said. ''But to get blown out like that ... it's infuriating.''
Edmonton coach Dave Tippett, who reunited McDavid and Draisaitl on his team's top line at the start of Monday's 3-2 victory over Ottawa, stuck with that combination and was rewarded. The league's No. 1 and 2 scorers helped the Oilers put together a fast start.
Nurse opened the scoring with his seventh of the season 3:52 into the first period. After Khaira made it 2-0 at 5:57, Draisaitl scored a power-play goal and McDavid made it 4-0 with his 16th goal with 6:34 left in the first.
Draisaitl added another power-play goal 7:01 into the second and scored his 14th goal at 7:35 in the third.
''We're trying to get our game back in order,'' Tippett said. ''Sometimes when you get punched in the mouth, you've got to come back and get up off the mat and start working again.
''That's what we've done.''
NOT BAD AT ALL
Smith stopped 21 shots to improve to 8-2-0 this season. He was working on his 42nd career shutout before Dadonov scored his 100th career goal 11:11 into the third.
After Friday's series finale, the Senators open a six-game homestand Sunday night against Toronto, and the Oilers begin a three-game trip at Vancouver on Saturday night.
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