The Oilers (25-22-4) earned their second straight win to finish a five-game homestand with a 3-2 record and move to within four points of a playoff spot. Columbus (21-26-5) suffered its first loss in five games. Raffi Torres scored twice for Edmonton, with Ryan Smyth and Petr Sykora registering the others.
David Vyborny and Fredrik Modin countered for Columbus.
Smyth opened the scoring at 3:31 of the first period on the power play. Columbus goalie Ty Conklin, a former Oiler, stopped Marc-Andre Bergeron's shot from the point but Smyth batted the rebound out of mid-air and into the net.
Pisani put Edmonton ahead 2-0 just 22 seconds into the second. Fernando Pisani feathered a nice pass through the legs of a Columbus defenceman to Torres, who scored to earn his 100th career point as an on Oiler.
Columbus made it 2-1 at 6:03 on the power play, deflecting a shot by former Oiler Anson Carter shot from the point past Edmonton starter Jussi Markkanen.
But Sykora countered with a power-play goal at 11:57. Smyth took a pass in the crease and chipped it to Sykora, who scored just his third goal in 17 games.
Markkanen made a huge stick save on Modin with just over a minute left to keep the score 3-1 heading into the third.
Columbus cut its deficit to 3-2 with Modin's power-play goal just 46 seconds into the third. But Edmonton restored its two-goal advantage at 5:41. Jarret Stoll raced to a puck behind the Columbus net and centred a pass to Torres, who beat Conklin for his second goal of the night.
Edmonton rounded out the scoring at 7:06 when Marty Reasoner set up Pisani.
The Oilers begin a two-game road trip in Vancouver on Thursday while the Blue Jackets head to Calgary to face the Flames on Friday.
NOTES: Markkanen was appearing in back-to-back games in the Oilers net for the first time since the sixth and seventh games of last year's Stanley Cup final . . . Conklin faced his former teammates for the first time . . . Columbus defenceman Bryan Berard played his first game of the season
Wednesday, returning from a lower back injury that had seen him sidelined for the entire season to this point . . . Wednesday's game was the 60th consecutive regular-season sellout of 16,839 at Rexall Place, a streak dating back to November 2005.