The slide coincided with a power-play drought that reached 28 chances before Vyborny's eighth goal forged a 2-2 tie. The Blue Jackets struck again with the man advantage when Cassels netted his ninth with 4:07 remaining in the period.
Columbus was three for eight for its 11th multiple power-play goal game of the season, surpassing the total from its first two seasons combined.
Pittsburgh's top-ranked power play was coming off a none-for-seven performance in Monday's 3-2 overtime loss to Atlanta. And even with the return of defenseman Dick Tarnstrom, it was just one of six with the man advantage against the NHL's top penalty-killing unit.
Without Tarnstrom, the Penguins endured a 10-game losing streak. But they came in with four wins in five games and appeared headed for another victory as Wayne Primeau and rookie Michal Sivek tallied in the opening 23 minutes.
Mike Sillinger's seventh goal halved the Blue Jackets' deficit midway through the second.
Geoff Sanderson added his 20th in the third period before Cassels got his second of the night into an empty net.