| 1 | Thu Oct 13 | vs Coyotes | W6-2 | 1-0-0 | 2 PTS | PPG Paints Arena · Pittsburgh, PA |
| 2 | Sat Oct 15 | vsLightning | W6-2 | 2-0-0 | 4 PTS | PPG Paints Arena · Pittsburgh, PA |
| 3 | Mon Oct 17 | atCanadiens | L2-3 (OT) | 2-0-1 | 5 PTS | Bell Centre · Montreal, QC |
| 4 | Thu Oct 20 | vsKings | W6-1 | 3-0-1 | 7 PTS | PPG Paints Arena · Pittsburgh, PA |
| 5 | Sat Oct 22 | atJackets | W6-3 | 4-0-1 | 9 PTS | Nationwide Arena · Columbus, OH |
| 6 | Mon Oct 24 | atOilers | L3-6 | 4-1-1 | 9 PTS | Rogers Place · Edmonton, AB |
| 7 | Tue Oct 25 | atFlames | L1-4 | 4-2-1 | 9 PTS | Scotiabank Saddledome · Calgary, Alberta |
| 8 | Fri Oct 28 | atCanucks | L1-5 | 4-3-1 | 9 PTS | Rogers Arena · Vancouver, British Columbia |
| 9 | Sat Oct 29 | atKraken | L1-3 | 4-4-1 | 9 PTS | Climate Pledge Arena · Seattle, WA |
| 10 | Tue Nov 1 | vsBruins | L5-6 (OT) | 4-4-2 | 10 PTS | PPG Paints Arena · Pittsburgh, PA |
| 11 | Wed Nov 2 | atSabres | L3-6 | 4-5-2 | 10 PTS | KeyBank Center · Buffalo, NY |
| 12 | Sat Nov 5 | vsKraken | L2-3 | 4-6-2 | 10 PTS | PPG Paints Arena · Pittsburgh, PA |
| 13 | Wed Nov 9 | atCapitals | W4-1 | 5-6-2 | 12 PTS | Capital One Arena · Washington, D.C. |
| 14 | Fri Nov 11 | atMaple Leafs | W4-2 | 6-6-2 | 14 PTS | Scotiabank Arena · Toronto, ON |
| 15 | Sat Nov 12 | atCanadiens | L4-5 (OT) | 6-6-3 | 15 PTS | Bell Centre · Montreal, QC |
| 16 | Tue Nov 15 | vsMaple Leafs | L2-5 | 6-7-3 | 15 PTS | PPG Paints Arena · Pittsburgh, PA |
| 17 | Thu Nov 17 | atWild | W6-4 | 7-7-3 | 17 PTS | Xcel Energy Center · St. Paul, MN |
| 18 | Sat Nov 19 | atJets | W3-0 | 8-7-3 | 19 PTS | Canada Life Centre · Winnipeg, Manitoba |
| 19 | Sun Nov 20 | atBlackhawks | W5-3 | 9-7-3 | 21 PTS | United Center · Chicago, IL |
| 20 | Wed Nov 23 | vsFlames | W2-1 (SO) | 10-7-3 | 23 PTS | PPG Paints Arena · Pittsburgh, PA |
| 21 | Fri Nov 25 | atFlyers | W4-1 | 11-7-3 | 25 PTS | Wells Fargo Center · Philadelphia, PA |
| 22 | Sat Nov 26 | vsMaple Leafs | L1-4 | 11-8-3 | 25 PTS | PPG Paints Arena · Pittsburgh, PA |
| 23 | Tue Nov 29 | vsHurricanes | L2-3 (OT) | 11-8-4 | 26 PTS | PPG Paints Arena · Pittsburgh, PA |
| 24 | Thu Dec 1 | vsKnights | W4-3 | 12-8-4 | 28 PTS | PPG Paints Arena · Pittsburgh, PA |
| 25 | Sat Dec 3 | vsBlues | W6-2 | 13-8-4 | 30 PTS | PPG Paints Arena · Pittsburgh, PA |
| 26 | Tue Dec 6 | vsJackets | W4-1 | 14-8-4 | 32 PTS | PPG Paints Arena · Pittsburgh, PA |
| 27 | Fri Dec 9 | atSabres | W4-3 (OT) | 15-8-4 | 34 PTS | KeyBank Center · Buffalo, NY |
| 28 | Sat Dec 10 | vsSabres | W3-1 | 16-8-4 | 36 PTS | PPG Paints Arena · Pittsburgh, PA |
| 29 | Mon Dec 12 | vsStars | W2-1 | 17-8-4 | 38 PTS | PPG Paints Arena · Pittsburgh, PA |
| 30 | Thu Dec 15 | atPanthers | W4-2 | 18-8-4 | 40 PTS | Amerant Bank Arena · Sunrise, FL |
| 31 | Sun Dec 18 | atHurricanes | L2-3 | 18-9-4 | 40 PTS | PNC Arena · Raleigh, NC |
| 32 | Tue Dec 20 | vsRangers | W3-2 | 19-9-4 | 42 PTS | PPG Paints Arena · Pittsburgh, PA |
| 33 | Thu Dec 22 | vsHurricanes | L3-4 (OT) | 19-9-5 | 43 PTS | PPG Paints Arena · Pittsburgh, PA |
| 34 | Tue Dec 27 | atIslanders | L1-5 | 19-10-5 | 43 PTS | UBS Arena · Elmont, NY |
| 35 | Wed Dec 28 | vsRed Wings | L4-5 (OT) | 19-10-6 | 44 PTS | PPG Paints Arena · Pittsburgh, PA |
| 36 | Fri Dec 30 | vsDevils | L2-4 | 19-11-6 | 44 PTS | PPG Paints Arena · Pittsburgh, PA |
| 37 | Mon Jan 2 | atBruins | L1-2 | 19-12-6 | 44 PTS | TD Garden · Boston, MA |
| 38 | Thu Jan 5 | atKnights | L2-5 | 19-13-6 | 44 PTS | T-Mobile Arena · Las Vegas, NV |
| 39 | Sun Jan 8 | atCoyotes | W4-1 | 20-13-6 | 46 PTS | Mullett Arena · Tempe, AZ |
| 40 | Tue Jan 10 | vsCanucks | W5-4 | 21-13-6 | 48 PTS | PPG Paints Arena · Pittsburgh, PA |
| 41 | Fri Jan 13 | vsJets | L1-4 | 21-14-6 | 48 PTS | PPG Paints Arena · Pittsburgh, PA |
| 42 | Sat Jan 14 | atHurricanes | L1-2 | 21-15-6 | 48 PTS | PNC Arena · Raleigh, NC |
| 43 | Mon Jan 16 | vsDucks | W4-3 (OT) | 22-15-6 | 50 PTS | PPG Paints Arena · Pittsburgh, PA |
| 44 | Wed Jan 18 | atSenators | L4-5 (OT) | 22-15-7 | 51 PTS | Canadian Tire Centre · Ottawa, ON |
| 45 | Fri Jan 20 | vsSenators | W4-1 | 23-15-7 | 53 PTS | PPG Paints Arena · Pittsburgh, PA |
| 46 | Sun Jan 22 | atDevils | L1-2 (OT) | 23-15-8 | 54 PTS | Prudential Center · Newark, NJ |
| 47 | Tue Jan 24 | vsPanthers | W7-6 (OT) | 24-15-8 | 56 PTS | PPG Paints Arena · Pittsburgh, PA |
| 48 | Thu Jan 26 | atCapitals | L2-3 (SO) | 24-15-9 | 57 PTS | Capital One Arena · Washington, D.C. |
| 49 | Sat Jan 28 | vsSharks | L4-6 | 24-16-9 | 57 PTS | PPG Paints Arena · Pittsburgh, PA |
| 50 | Tue Feb 7 | vsAvalanche | W2-1 (OT) | 25-16-9 | 59 PTS | PPG Paints Arena · Pittsburgh, PA |
| 51 | Fri Feb 10 | atDucks | W6-3 | 26-16-9 | 61 PTS | Honda Center · Anaheim, CA |
| 52 | Sat Feb 11 | atKings | L0-6 | 26-17-9 | 61 PTS | Crypto.com Arena · Los Angeles, CA |
| 53 | Tue Feb 14 | atSharks | W3-1 | 27-17-9 | 63 PTS | SAP Center · San Jose, CA |
| 54 | Fri Feb 17 | atIslanders | L4-5 | 27-18-9 | 63 PTS | UBS Arena · Elmont, NY |
| 55 | Sat Feb 18 | vsDevils | L2-5 | 27-19-9 | 63 PTS | PPG Paints Arena · Pittsburgh, PA |
| 56 | Mon Feb 20 | vsIslanders | L2-4 | 27-20-9 | 63 PTS | PPG Paints Arena · Pittsburgh, PA |
| 57 | Thu Feb 23 | vsOilers | L2-7 | 27-21-9 | 63 PTS | PPG Paints Arena · Pittsburgh, PA |
| 58 | Sat Feb 25 | atBlues | W3-2 (OT) | 28-21-9 | 65 PTS | Enterprise Center · St. Louis, MO |
| 59 | Sun Feb 26 | vsLightning | W7-3 | 29-21-9 | 67 PTS | PPG Paints Arena · Pittsburgh, PA |
| 60 | Tue Feb 28 | atPredators | W3-1 | 30-21-9 | 69 PTS | Bridgestone Arena · Nashville, TN |
| 61 | Thu Mar 2 | atLightning | W5-4 (OT) | 31-21-9 | 71 PTS | AMALIE Arena · Tampa, FL |
| 62 | Sat Mar 4 | atPanthers | L1-4 | 31-22-9 | 71 PTS | Amerant Bank Arena · Sunrise, FL |
| 63 | Tue Mar 7 | vsJackets | W5-4 (OT) | 32-22-9 | 73 PTS | PPG Paints Arena · Pittsburgh, PA |
| 64 | Thu Mar 9 | vsIslanders | L3-4 (OT) | 32-22-10 | 74 PTS | PPG Paints Arena · Pittsburgh, PA |
| 65 | Sat Mar 11 | vsFlyers | W5-1 | 33-22-10 | 76 PTS | PPG Paints Arena · Pittsburgh, PA |
| 66 | Sun Mar 12 | vsRangers | W3-2 (OT) | 34-22-10 | 78 PTS | PPG Paints Arena · Pittsburgh, PA |
| 67 | Tue Mar 14 | vsCanadiens | L4-6 | 34-23-10 | 78 PTS | PPG Paints Arena · Pittsburgh, PA |
| 68 | Thu Mar 16 | atRangers | L2-4 | 34-24-10 | 78 PTS | Madison Square Garden · Manhattan, NY |
| 69 | Sat Mar 18 | atRangers | L0-6 | 34-25-10 | 78 PTS | Madison Square Garden · Manhattan, NY |
| 70 | Mon Mar 20 | vsSenators | L1-2 | 34-26-10 | 78 PTS | PPG Paints Arena · Pittsburgh, PA |
| 71 | Wed Mar 22 | atAvalanche | W5-2 | 35-26-10 | 80 PTS | Ball Arena · Denver, CO |
| 72 | Thu Mar 23 | atStars | L2-3 | 35-27-10 | 80 PTS | American Airlines Center · Dallas, TX |
| 73 | Sat Mar 25 | vsCapitals | W4-3 | 36-27-10 | 82 PTS | PPG Paints Arena · Pittsburgh, PA |
| 74 | Tue Mar 28 | atRed Wings | L4-7 | 36-28-10 | 82 PTS | Little Caesars Arena · Detroit, MI |
| 75 | Thu Mar 30 | vsPredators | W2-0 | 37-28-10 | 84 PTS | PPG Paints Arena · Pittsburgh, PA |
| 76 | Sat Apr 1 | vsBruins | L3-4 | 37-29-10 | 84 PTS | PPG Paints Arena · Pittsburgh, PA |
| 77 | Sun Apr 2 | vsFlyers | W4-2 | 38-29-10 | 86 PTS | PPG Paints Arena · Pittsburgh, PA |
| 78 | Tue Apr 4 | atDevils | L1-5 | 38-30-10 | 86 PTS | Prudential Center · Newark, NJ |
| 79 | Thu Apr 6 | vsWild | W4-1 | 39-30-10 | 88 PTS | PPG Paints Arena · Pittsburgh, PA |
| 80 | Sat Apr 8 | atRed Wings | W5-1 | 40-30-10 | 90 PTS | Little Caesars Arena · Detroit, MI |
| 81 | Tue Apr 11 | vsBlackhawks | L2-5 | 40-31-10 | 90 PTS | PPG Paints Arena · Pittsburgh, PA |
| 82 | Thu Apr 13 | atJackets | L2-3 (OT) | 40-31-11 | 91 PTS | Nationwide Arena · Columbus, OH |
