After rallying to erase an early two-goal deficit, the Flames fell 4-3 in overtime to the Penguins in Pittsburgh on Monday.
Justin Schultz one-timed a pass from Phil Kessel past goalie Jon Gillies at 2:36 of the extra session to lead the two-time defending Stanley Cup champions to victory.
Earlier in OT, Johnny Gaudreau had a breakaway, but couldn't slip the puck past Pittsburgh goalie Tristan Jarry.
"Going into overtime, it could be anybody's game," said Flames coach Glen Gulutzan. "When you've got that many dangerous guys on the ice with that much room, somebody's going to end it and it just happened to be them on that next chance."
Troy Brouwer led Calgary (32-25-10) with a goal and an assist, while Mark Giordano and Mikael Backlund also found the back of the net.
"Good resiliency of this team making sure that we got a point tonight," Brouwer said. "Obviously, we would have liked to get the second one, but overall I actually thought we played a fairly decent game and well enough to get points."
After allowing two early goals, Gillies settled down and finished with 28 saves to help the Flames get a point.
"You've got to start somewhere and it's a building spot," said Gulutzan in regards to the OT setback. "Had we come out here with a point and got outchanced 23-9, I don't know how much of a springboard you get, but when you come in here and play well and you outshoot them and you don't come out with it in overtime, it's still a building block."
Evgeni Malkin had a goal and two assists for the Penguins (38-25-4), while Chad Ruhwedel and Kris Letang also scored and Jarry finished with 35 saves.
Ruhwedel opened the scoring for the Penguins at 2:10 of the first period when his point shot through traffic found its way into the back of the net behind Gillies.
The Penguins went up 2-0 just 55 seconds later on a goal by Malkin, who intercepted a clearing attempt from Gillies behind the net before tucking the puck into a wide-open net.
"Malkin picks it out of the air with his stick, so not much you could do there," said Gulutzan, who liked the way his team bounced back after surrendering the two early goals. "I thought our response, though, right after was real good. It showed a lot of character and resilience. I thought from then on we had a pretty good road game."
Giordano pulled the Flames back within a goal at 6:14 of the first when he snapped a shot into the top corner over the left shoulder of Jarry, who was screened by Curtis Lazar on the play.
Backlund then scored a highlight-reel goal 4:04 later when he made a nice toe-drag move to get around Letang before making another quick deke and backhanding a shot past Jarry.
"We just kept going and kept pushing and eventually we got rewarded and came back," Backlund said.
Just past the nine-minute mark of the second stanza, the Flames had a great chance to take their first lead of the game, but Jarry kicked out his left pad to stop a shot fired his way by Mark Jankowski, who one-timed a pass from linemate Garnet Hathaway on net.
Letang then put the home team back up by a goal at 17:01 when he jumped up into the play and took a pass from Malkin before snapping a shot past Gillies.
"That third goal can't go in on me," Gillies said. "I tried to centre shift into it and it just got through my arm. That just can't happen at this time of the year, so that one's on me. I was thankful that we were able to get it back and at least get a point."
TJ Brodie did a great job to draw the Flames even once again with 2.4 seconds left before the second intermission. Brodie drove hard to the net before sliding a pass into the slot to Brouwer, who made no mistake in finding the back of the net.
The Flames and Penguins traded chances just past the eight-minute mark of the third period as Jarry stuck out his left pad to turn aside a shot by Matthew Tkachuk before Gillies stood his ground to stop a shot fired his way by Phil Kessel.
Left-winger Micheal Ferland returned to Calgary's lineup after missing the past four games with a lower-body injury … In 10 career games against the Penguins, Backlund has recorded three goals and five assists for eight points … Heading into Monday's matchup, the Flames had won five in a row against the Penguins, including the last three in either overtime or a shootout.
The Flames will wrap up their quick three-game road trip with games against the Buffalo Sabres on Wednesday (5:30 p.m. MT, TV: Sportsnet West , RADIO: Sportsnet 960 The FAN) and the Ottawa Senators two nights later (5:30 p.m. MT, TV: Sportsnet West, RADIO: Sportsnet 960 The FAN).