Logan Couture, with his franchise rookie-record tying 25th goal of the season, also scored while Antti Niemi stopped 24 shots. Improving to 14-2-1 in their past 17 games, the surging Sharks vaulted a point ahead of Phoenix to take over the Pacific Division lead.
Tyler Kennedy scored twice for the Penguins, including tying the game by stuffing in Jordan Staal's rebound, with 50 seconds remaining in the third period.
Marleau scored the decisive goal during a scramble in front, and after Marc-Andre Fleury stopped Couture from in close. The rebound dribbled to the left of the net, where Marleau flipped it in.
The goal was payback for Marleau, who was in on a breakaway a minute earlier, only to be robbed by Fleury's brilliant glove save.
The Penguins are winless in their past three (0-1-2) and dropped to 2-5-2 in their past nine since Evgeni Malkin sustained a season-ending knee injury to join captain Sidney Crosby on the injury list. Crosby is out indefinitely after missing his 21st straight game with a concussion.
The Penguins might be down yet another key player after defenseman Brooks Orpik did not return for the start of the second period after taking Marleau's shot off his hand late in the opening period. Orpik skated off shaking his hand and was escorted up the tunnel. The Penguins had no update on his status during the game.
Pittsburgh squandered a 1-0 lead and was forced to rally in the final minute, and with Fleury pulled for an extra attacker. Staal was set up to the right of the net, where he got a shot off that hit Niemi, then the post and settled in the crease, where Kennedy crashed to stuff it in at 19:10.
The Sharks, coming off a 4-3 win at Detroit on Tuesday, won by rallying from a 1-0 deficit, after Kennedy opened the scoring during a scramble in front at 5:48 of the first.
Couture tied it 3:01 into the second period. He's tied with the Islanders' Michael Grabner for the rookie lead in goals and also tied the franchise rookie record set by Pat Falloon in 1991. Marleau then scored 5:28 into the third period to put the Sharks ahead 2-1.
The new-look Penguins continue to have difficulty scoring, despite shaking up their lineup by adding forward James Neal and defenseman Matt Niskanen in a trade that sent defenseman Alex Goligoski to Dallas on Monday.
Both Neal and Niskanen made their debuts, but the Penguins extended their string to 15 games since scoring four or more goals in regulation.
Pittsburgh has been shut out three times during that span, including a 1-0 loss to Washington on Monday.
Niemi was solid in preserving the victory. A minute into the third period, he got his right shoulder up to stop Neal's hard shot from just inside the blue line. He made an even better save with 7:01 left, getting his glove up to snatch a snap shot from Kris Letang, who was driving in alone up the right wing.
Fleury kept the Penguins in the game. He finished with 35 saves, including a pair of blocker shots on bang-bang chances from Joe Pavelski and Kyle Wellwood with 4 minutes left.
Notes: In closing a brief two-game homestand, the Penguins hit the road for a five-game swing that opens at Carolina on Friday. The home games are the only two for Pittsburgh during a 25-day span. ... The Sharks conclude a three-game road trip at Calgary on Friday before returning home for a six-game homestand, which opens Tuesday against Colorado. ... For the second consecutive home game, the start of the second period was delayed because the house lights wouldn't come on in the first-year Consol Energy Center. The delay on Wednesday lasted more than 15 minutes, or 10 minutes longer than on Monday.