The Penguins (8-8-4), who ended a four-game losing streak, were 0-2-1 without Crosby. They were 1-7-2 in their previous 10 games.
DeSmith made 18 saves for Pittsburgh.
"We obviously came out flying. I'm happy we did, obviously," DeSmith said. "We jumped out to a big lead. I think that's something that we really needed to get the momentum. We just kind of rode it."
Anton Khudobin made 11 saves on 16 shots for Dallas (11-9-2) before being replaced by Landon Bow at 8:52 of the second period. Bow made the save on all 14 shots he faced in his NHL debut.
Khudobin had a simple explanation for what he could've done better.
"Stop more pucks. Sometimes make more saves," Khudobin said. "It didn't happen tonight."
Crosby backhanded a pass to Guentzel, who one-timed it through Khudobin's five-hole to make it 1-0 at 3:58 of the first. It was Guentzel's eighth goal of the season and third in his past five games.
Malkin extended it to 2-0 on the power play by shooting past Khudobin's blocker at 6:06.
Crosby made it 3-0 after carrying the puck down the right wall and using one hand to control the puck while holding off Esa Lindell and turning toward the net. He backhanded a shot on net before kicking the rebound to his stick and shooting over Khudobin's right pad at 10:04.
After Olli Maatta shot into the crease, Hornqvist scored on the rebound to make it 4-0 at 3:20 of the second.
Pearson scored for the second straight game with a slap shot past Khudobin, pushing the lead to 5-0 at 8:52.
Roope Hintz cut it to 5-1 at 7:55 of the third for the Stars.
"All we needed to do was go out there in the third, show a little pride and show a little character," Stars forward Jamie Benn said. "Pretty embarrassing tonight. I think we let our goalie down, and we let each other down. Tough night."