Kris Letang proved the hero as he scored the go-ahead goal seven minutes, 46 seconds into the second period on Sunday, after Logan Couture cancelled out Brian Dumoulin's power-play goal 8:16 into the first period.
Patric Hornqvist sealed the win and Pittsburgh's 4-2 series triumph with a goal 18:58 into the third period.
The Penguins sealed the Stanley Cup Final series in enemy territory at the Sharks' SAP Center, after San Jose had rallied to push the series to a sixth game on Thursday.
But Pittsburgh would not be denied again, as they shut the series down with a professional performance to claim a second Stanley Cup championship in seven years.
The win caps off a tremendous season for the Penguins and coach Mike Sullivan, who replaced Mike Johnston on December 12 after the latter posted a 15-10-3 record through 28 games this term.
Sullivan arrived from American Hockey League outfit Wilkes-Barre/Scranton Penguins, steering Pittsburgh to second place in the Metropolitan Division, with a record of 48-26-8 before knocking off the New York Rangers, President's Cup winners the Washington Capitals and the Tampa Bay Lightning to win the Eastern Conference.
Now, they have won the biggest of the lot.
The Sharks, who made the finals from third in the Pacific Division, were chasing a first ever Stanley Cup title, but could not stop the Penguins.
Up until game six, they even boasted four of the top five skaters in the post-season, with Couture (29 points in 23 games), Joe Pavelski (23 points in 23 games), Brent Burns (23 points in 23 games) and Joe Thornton (21 points in 23 games) all having huge play-off campaigns.
Nevertheless, it was the collective effort of the Penguins that won the day and the series as they claimed their fourth Stanley Cup triumph.