Mercer tied it 1-1 at 4:53. A rebound off an initial backhand from Mercer went past Hischier, battling with Pittsburgh forward Jeff Carter at the left post, to Mercer for another backhand from just outside the crease.
Dougie Hamilton gave the Devils a 2-1 lead on the power play at 3:47 of the second period, scoring with a one-timer after Hischier carried the puck around the back of the net and fed him in the right face-off circle.
Hischier scored short-handed for his 100th goal to make it 3-1 at 8:25. After tapping the puck past Pittsburgh defenseman Kris Letang at the opposite blue line for a 2-on-1, Hischier took a backhand pass from Yegor Sharangovich for a wrist shot to the left of the net.
Jesper Bratt extended the lead to 4-1 at 8:39 of the third period on a one-timer off a pass from Hughes.
"Felt fine. Probably tired," Hughes said. "Not my best, but you know, you miss a week or two and we had the All-Star break too, so really that's one goal in pretty much two or three weeks. That's a good start and it's a really big win for our team."