| 1 | Wed Oct 9 | vs Rangers | L0-6 | 0-1-0 | 0 PTS | PPG Paints Arena · Pittsburgh, PA |
| 2 | Thu Oct 10 | at Red Wings | W6-3 | 1-1-0 | 2 PTS | Little Caesars Arena · Detroit, MI |
| 3 | Sat Oct 12 | at Maple Leafs | L2-4 | 1-2-0 | 2 PTS | Scotiabank Arena · Toronto, ON |
| 4 | Mon Oct 14 | at Canadiens | W6-3 | 2-2-0 | 4 PTS | Bell Centre · Montreal, QC |
| 5 | Wed Oct 16 | vs Sabres | W6-5 (OT) | 3-2-0 | 6 PTS | PPG Paints Arena · Pittsburgh, PA |
| 6 | Fri Oct 18 | vs Hurricanes | L1-4 | 3-3-0 | 6 PTS | PPG Paints Arena · Pittsburgh, PA |
| 7 | Sun Oct 20 | at Jets | L3-6 | 3-4-0 | 6 PTS | Canada Life Centre · Winnipeg, Manitoba |
| 8 | Tue Oct 22 | at Flames | L3-4 (SO) | 3-4-1 | 7 PTS | Scotiabank Saddledome · Calgary, Alberta |
| 9 | Fri Oct 25 | at Oilers | L0-4 | 3-5-1 | 7 PTS | Rogers Place · Edmonton, AB |
| 10 | Sat Oct 26 | at Canucks | L3-4 | 3-6-1 | 7 PTS | Rogers Arena · Vancouver, British Columbia |
| 11 | Tue Oct 29 | vs Wild | L3-5 | 3-7-1 | 7 PTS | PPG Paints Arena · Pittsburgh, PA |
| 12 | Thu Oct 31 | vs Ducks | W2-1 (OT) | 4-7-1 | 9 PTS | PPG Paints Arena · Pittsburgh, PA |
| 13 | Sat Nov 2 | vsCanadiens | W3-1 | 5-7-1 | 11 PTS | PPG Paints Arena · Pittsburgh, PA |
| 14 | Tue Nov 5 | at Islanders | L3-4 (SO) | 5-7-2 | 12 PTS | UBS Arena · Elmont, NY |
| 15 | Thu Nov 7 | atHurricanes | L1-5 | 5-8-2 | 12 PTS | PNC Arena · Raleigh, NC |
| 16 | Fri Nov 8 | at Capitals | W4-2 | 6-8-2 | 14 PTS | Capital One Arena · Washington, D.C. |
| 17 | Mon Nov 11 | vs Stars | L1-7 | 6-9-2 | 14 PTS | PPG Paints Arena · Pittsburgh, PA |
| 18 | Wed Nov 13 | vsRed Wings | L2-3 (OT) | 6-9-3 | 15 PTS | PPG Paints Arena · Pittsburgh, PA |
| 19 | Fri Nov 15 | at Jackets | L2-6 | 6-10-3 | 15 PTS | Nationwide Arena · Columbus, OH |
| 20 | Sat Nov 16 | vs Sharks | W4-3 (SO) | 7-10-3 | 17 PTS | PPG Paints Arena · Pittsburgh, PA |
| 21 | Tue Nov 19 | vs Lightning | L2-3 (OT) | 7-10-4 | 18 PTS | PPG Paints Arena · Pittsburgh, PA |
| 22 | Fri Nov 22 | vsJets | L1-4 | 7-11-4 | 18 PTS | PPG Paints Arena · Pittsburgh, PA |
| 23 | Sat Nov 23 | vs Utah HC | L1-6 | 7-12-4 | 18 PTS | PPG Paints Arena · Pittsburgh, PA |
| 24 | Wed Nov 27 | vsCanucks | W5-4 | 8-12-4 | 20 PTS | PPG Paints Arena · Pittsburgh, PA |
| 25 | Fri Nov 29 | at Bruins | W2-1 | 9-12-4 | 22 PTS | TD Garden · Boston, MA |
| 26 | Sat Nov 30 | vsFlames | W6-2 | 10-12-4 | 24 PTS | PPG Paints Arena · Pittsburgh, PA |
| 27 | Tue Dec 3 | vs Panthers | W5-4 (OT) | 11-12-4 | 26 PTS | PPG Paints Arena · Pittsburgh, PA |
| 28 | Fri Dec 6 | atRangers | L2-4 | 11-13-4 | 26 PTS | Madison Square Garden · Manhattan, NY |
| 29 | Sat Dec 7 | vsMaple Leafs | W5-2 | 12-13-4 | 28 PTS | PPG Paints Arena · Pittsburgh, PA |
| 30 | Tue Dec 10 | vs Avalanche | L2-6 | 12-14-4 | 28 PTS | PPG Paints Arena · Pittsburgh, PA |
| 31 | Thu Dec 12 | atCanadiens | W9-2 | 13-14-4 | 30 PTS | Bell Centre · Montreal, QC |
| 32 | Sat Dec 14 | at Senators | L2-3 (OT) | 13-14-5 | 31 PTS | Canadian Tire Centre · Ottawa, ON |
| 33 | Tue Dec 17 | vs Kings | W3-2 (OT) | 14-14-5 | 33 PTS | PPG Paints Arena · Pittsburgh, PA |
| 34 | Thu Dec 19 | at Predators | W5-4 (OT) | 15-14-5 | 35 PTS | Bridgestone Arena · Nashville, TN |
| 35 | Sat Dec 21 | at Devils | L0-3 | 15-15-5 | 35 PTS | Prudential Center · Newark, NJ |
| 36 | Mon Dec 23 | vs Flyers | W7-3 | 16-15-5 | 37 PTS | PPG Paints Arena · Pittsburgh, PA |
| 37 | Sat Dec 28 | atIslanders | L3-6 | 16-16-5 | 37 PTS | UBS Arena · Elmont, NY |
| 38 | Sun Dec 29 | vsIslanders | W3-2 | 17-16-5 | 39 PTS | PPG Paints Arena · Pittsburgh, PA |
| 39 | Tue Dec 31 | atRed Wings | L2-4 | 17-17-5 | 39 PTS | Little Caesars Arena · Detroit, MI |
| 40 | Fri Jan 3 | atPanthers | L2-3 (SO) | 17-17-6 | 40 PTS | Amerant Bank Arena · Sunrise, FL |
| 41 | Sun Jan 5 | atHurricanes | L3-4 (OT) | 17-17-7 | 41 PTS | PNC Arena · Raleigh, NC |
| 42 | Tue Jan 7 | vsJackets | L3-4 (SO) | 17-17-8 | 42 PTS | PPG Paints Arena · Pittsburgh, PA |
| 43 | Thu Jan 9 | vsOilers | W5-3 | 18-17-8 | 44 PTS | PPG Paints Arena · Pittsburgh, PA |
| 44 | Sat Jan 11 | vsSenators | L0-5 | 18-18-8 | 44 PTS | PPG Paints Arena · Pittsburgh, PA |
| 45 | Sun Jan 12 | vsLightning | L2-5 | 18-19-8 | 44 PTS | PPG Paints Arena · Pittsburgh, PA |
| 46 | Tue Jan 14 | vs Kraken | L2-4 | 18-20-8 | 44 PTS | PPG Paints Arena · Pittsburgh, PA |
| 47 | Fri Jan 17 | atSabres | W5-2 | 19-20-8 | 46 PTS | KeyBank Center · Buffalo, NY |
| 48 | Sat Jan 18 | atCapitals | L1-4 | 19-21-8 | 46 PTS | Capital One Arena · Washington, D.C. |
| 49 | Mon Jan 20 | atKings | W5-1 | 20-21-8 | 48 PTS | Crypto.com Arena · Los Angeles, CA |
| 50 | Thu Jan 23 | atDucks | L1-5 | 20-22-8 | 48 PTS | Honda Center · Anaheim, CA |
| 51 | Sat Jan 25 | atKraken | L1-4 | 20-23-8 | 48 PTS | Climate Pledge Arena · Seattle, WA |
| 52 | Mon Jan 27 | atSharks | L1-2 | 20-24-8 | 48 PTS | SAP Center · San Jose, CA |
| 53 | Wed Jan 29 | atUtah HC | W3-2 (OT) | 21-24-8 | 50 PTS | Delta Center · Salt Lake City, UT |
| 54 | Sat Feb 1 | vsPredators | W3-0 | 22-24-8 | 52 PTS | PPG Paints Arena · Pittsburgh, PA |
| 55 | Tue Feb 4 | vsDevils | L2-3 (SO) | 22-24-9 | 53 PTS | PPG Paints Arena · Pittsburgh, PA |
| 56 | Fri Feb 7 | atRangers | W3-2 | 23-24-9 | 55 PTS | Madison Square Garden · Manhattan, NY |
| 57 | Sat Feb 8 | atFlyers | L2-3 | 23-25-9 | 55 PTS | Wells Fargo Center · Philadelphia, PA |
| 58 | Sat Feb 22 | vsCapitals | L3-8 | 23-26-9 | 55 PTS | PPG Paints Arena · Pittsburgh, PA |
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