Fedorov completed his natural hat trick on a classic give-and-go with Brendan Shanahan 9:42 into the second. After dropping the puck for Shanahan in the right faceoff circle, Fedorov skated left and went to the net.
The entire Pittsburgh defense followed Shanahan, who passed to Fedorov at the far goalpost for an easy tally after Jean-Sebastien Aubin followed his teammates in abandoning that side of the rink.
"Playing with Brett Hull and Brendan makes it a little bit easier because those guys are really good players and they can pass the puck very well," Fedorov said. "All I need to do is just skate and be there at the right time for them."
Hull assisted on two of Fedorov's goals for his second multi-point game of the year. He had 19 last season.
The hat trick was Fedorov's first since November 22, 2000 in a 5-4 loss to the Boston Bruins. No Detroit player has had a three-goal game at Joe Louis Arena since then, although Hull had a hat trick on January 26 at St. Louis.
"He was awesome," said Penguins center Mario Lemieux, who has 40 career hat tricks. "The way he skates, he's just dominating out there. Especially in the neutral zone, he picks up a lot of speed. You can't defend against that. He took over the game and played great tonight."
Fedorov recorded his fifth career hat trick. There have been 226 hat tricks in Red Wings history.
"Certainly, you want to play your best game, especially when you match up with a center like Mario," Fedorov said.
After Detroit fell behind, 1-0, in the first period, Luc Robitaille scored a pair of goals 53 seconds apart to give the Red Wings the lead for good. Robitaille's last two-goal game was March 9 at St. Louis.
"Luc, he finally found some spots that he was going to and now the puck was there when he was there," Red Wings coach Dave Lewis said. "So that was good for him to get two, also."
Alexei Kovalev had given Pittsburgh the lead 7:53 into the game with an excellent individual play. He skated around Mathieu Dandenault's check at the blue line, then skated freely through Detroit's zone to the inside of the right faceoff circle where he launched a slap shot past Manny Legace.
Kovalev added a power-play goal with 16 seconds left in the second period for his second consecutive two-goal game. He tallied a pair in a 3-3 tie at Montreal on Tuesday.
Legace, who made 24 saves, gave starter Curtis Joseph a rest in advance of Saturday's game at Nashville.
"My gut was turning all afternoon," Legace said. "It was hard to eat lunch today, knowing that Lemieux was going to be out there. It's just so scary. I caught myself watching him the whole time. Just the magic that man can develop in a matter of seconds, it was kind of scary."
Lemieux did not score his 659th career goal against Legace, but he did have two asssists and continues to hold the league lead with 12.
"My dream, pretty much since I was a little kid, (was) playing against Mario," said Red Wings defenseman Jiri Fischer, who had a goal and two assists. "He's definitely the best forward I've been against on the ice, ever."
The Penguins got as close as 5-3 on Ville Nieminen's goal 4:53 into the third period, but Fischer answered 41 seconds later for the Red Wings.
Igor Larianov passed from the top of the right circle to Fischer at the left post. Again, Aubin was nowhere to be found when the puck came to an open man at the side of his net.
"We make 5-3, they come back and make it 6-3," Penguins coach Rick Kehoe said. "There were a ton of points where in situations like that we have to do better."
Aubin made 37 saves as the Penguins were outshot, 44-27. Legace got his second win in as many starts this season.
The Red Wings scored seven goals for the first time since an 8-3 rout of Minnesota on November 16 last season.