| 1 | Tue Oct 12 | at Lightning | W6-2 | 1-0-0 | 2 PTS | AMALIE Arena · Tampa, FL |
| 2 | Thu Oct 14 | atPanthers | L4-5 (OT) | 1-0-1 | 3 PTS | Amerant Bank Arena · Sunrise, FL |
| 3 | Sat Oct 16 | vsBlackhawks | W5-2 | 2-0-1 | 5 PTS | PPG Paints Arena · Pittsburgh, PA |
| 4 | Tue Oct 19 | vsStars | L1-2 (SO) | 2-0-2 | 6 PTS | PPG Paints Arena · Pittsburgh, PA |
| 5 | Sat Oct 23 | vsMaple Leafs | W7-1 | 3-0-2 | 8 PTS | PPG Paints Arena · Pittsburgh, PA |
| 6 | Tue Oct 26 | vsLightning | L1-5 | 3-1-2 | 8 PTS | PPG Paints Arena · Pittsburgh, PA |
| 7 | Thu Oct 28 | vsFlames | L0-4 | 3-2-2 | 8 PTS | PPG Paints Arena · Pittsburgh, PA |
| 8 | Sat Oct 30 | vsDevils | L2-4 | 3-3-2 | 8 PTS | PPG Paints Arena · Pittsburgh, PA |
| 9 | Thu Nov 4 | vsFlyers | W3-2 (OT) | 4-3-2 | 10 PTS | PPG Paints Arena · Pittsburgh, PA |
| 10 | Sat Nov 6 | vsWild | L4-5 (SO) | 4-3-3 | 11 PTS | PPG Paints Arena · Pittsburgh, PA |
| 11 | Tue Nov 9 | atBlackhawks | L2-3 (SO) | 4-3-4 | 12 PTS | United Center · Chicago, IL |
| 12 | Thu Nov 11 | vsPanthers | W3-2 (SO) | 5-3-4 | 14 PTS | PPG Paints Arena · Pittsburgh, PA |
| 13 | Sat Nov 13 | atSenators | L3-6 | 5-4-4 | 14 PTS | Canadian Tire Centre · Ottawa, ON |
| 14 | Sun Nov 14 | atCapitals | L1-6 | 5-5-4 | 14 PTS | Capital One Arena · Washington, D.C. |
| 15 | Tue Nov 16 | vsSabres | L1-2 | 5-6-4 | 14 PTS | PPG Paints Arena · Pittsburgh, PA |
| 16 | Thu Nov 18 | atCanadiens | W6-0 | 6-6-4 | 16 PTS | Bell Centre · Montreal, QC |
| 17 | Sat Nov 20 | atMaple Leafs | W2-0 | 7-6-4 | 18 PTS | Scotiabank Arena · Toronto, ON |
| 18 | Mon Nov 22 | atJets | W3-1 | 8-6-4 | 20 PTS | Canada Life Centre · Winnipeg, Manitoba |
| 19 | Wed Nov 24 | vsCanucks | W4-1 | 9-6-4 | 22 PTS | PPG Paints Arena · Pittsburgh, PA |
| 20 | Fri Nov 26 | atIslanders | W1-0 | 10-6-4 | 24 PTS | UBS Arena · Elmont, NY |
| 21 | Sat Nov 27 | vsCanadiens | L3-6 | 10-7-4 | 24 PTS | PPG Paints Arena · Pittsburgh, PA |
| 22 | Mon Nov 29 | atFlames | L1-2 (SO) | 10-7-5 | 25 PTS | Scotiabank Saddledome · Calgary, Alberta |
| 23 | Wed Dec 1 | atOilers | L2-5 | 10-8-5 | 25 PTS | Rogers Place · Edmonton, AB |
| 24 | Sat Dec 4 | atCanucks | W4-1 | 11-8-5 | 27 PTS | Rogers Arena · Vancouver, British Columbia |
| 25 | Mon Dec 6 | atKraken | W6-1 | 12-8-5 | 29 PTS | Climate Pledge Arena · Seattle, WA |
| 26 | Fri Dec 10 | atCapitals | W4-2 | 13-8-5 | 31 PTS | Capital One Arena · Washington, D.C. |
| 27 | Sat Dec 11 | vsDucks | W1-0 | 14-8-5 | 33 PTS | PPG Paints Arena · Pittsburgh, PA |
| 28 | Tue Dec 14 | vsCanadiens | W5-2 | 15-8-5 | 35 PTS | PPG Paints Arena · Pittsburgh, PA |
| 29 | Fri Dec 17 | vsSabres | W3-2 (OT) | 16-8-5 | 37 PTS | PPG Paints Arena · Pittsburgh, PA |
| 30 | Sun Dec 19 | atDevils | W3-2 | 17-8-5 | 39 PTS | Prudential Center · Newark, NJ |
| 31 | Sun Jan 2 | vsSharks | W8-5 | 18-8-5 | 41 PTS | PPG Paints Arena · Pittsburgh, PA |
| 32 | Wed Jan 5 | vsBlues | W5-3 | 19-8-5 | 43 PTS | PPG Paints Arena · Pittsburgh, PA |
| 33 | Thu Jan 6 | atFlyers | W6-2 | 20-8-5 | 45 PTS | Wells Fargo Center · Philadelphia, PA |
| 34 | Sat Jan 8 | atStars | L2-3 | 20-9-5 | 45 PTS | American Airlines Center · Dallas, TX |
| 35 | Tue Jan 11 | atDucks | W4-1 | 21-9-5 | 47 PTS | Honda Center · Anaheim, CA |
| 36 | Thu Jan 13 | atKings | L2-6 | 21-10-5 | 47 PTS | Crypto.com Arena · Los Angeles, CA |
| 37 | Sat Jan 15 | atSharks | W2-1 (OT) | 22-10-5 | 49 PTS | SAP Center · San Jose, CA |
| 38 | Mon Jan 17 | atKnights | W5-3 | 23-10-5 | 51 PTS | T-Mobile Arena · Las Vegas, NV |
| 39 | Thu Jan 20 | vsSenators | W6-4 | 24-10-5 | 53 PTS | PPG Paints Arena · Pittsburgh, PA |
| 40 | Fri Jan 21 | atJackets | W5-2 | 25-10-5 | 55 PTS | Nationwide Arena · Columbus, OH |
| 41 | Sun Jan 23 | vsJets | W3-2 (SO) | 26-10-5 | 57 PTS | PPG Paints Arena · Pittsburgh, PA |
| 42 | Tue Jan 25 | vsCoyotes | W6-3 | 27-10-5 | 59 PTS | PPG Paints Arena · Pittsburgh, PA |
| 43 | Thu Jan 27 | vsKraken | L1-2 (OT) | 27-10-6 | 60 PTS | PPG Paints Arena · Pittsburgh, PA |
| 44 | Fri Jan 28 | vsRed Wings | L2-3 (SO) | 27-10-7 | 61 PTS | PPG Paints Arena · Pittsburgh, PA |
| 45 | Sun Jan 30 | vsKings | L3-4 | 27-11-7 | 61 PTS | PPG Paints Arena · Pittsburgh, PA |
| 46 | Tue Feb 1 | vsCapitals | L3-4 (OT) | 27-11-8 | 62 PTS | PPG Paints Arena · Pittsburgh, PA |
| 47 | Tue Feb 8 | atBruins | W4-2 | 28-11-8 | 64 PTS | TD Garden · Boston, MA |
| 48 | Thu Feb 10 | atSenators | W2-0 | 29-11-8 | 66 PTS | Canadian Tire Centre · Ottawa, ON |
| 49 | Sun Feb 13 | atDevils | W4-2 | 30-11-8 | 68 PTS | Prudential Center · Newark, NJ |
| 50 | Tue Feb 15 | vsFlyers | W5-4 (OT) | 31-11-8 | 70 PTS | PPG Paints Arena · Pittsburgh, PA |
| 51 | Thu Feb 17 | atMaple Leafs | L1-4 | 31-12-8 | 70 PTS | Scotiabank Arena · Toronto, ON |
| 52 | Sun Feb 20 | vsHurricanes | L3-4 | 31-13-8 | 70 PTS | PPG Paints Arena · Pittsburgh, PA |
| 53 | Thu Feb 24 | vsDevils | L1-6 | 31-14-8 | 70 PTS | PPG Paints Arena · Pittsburgh, PA |
| 54 | Sat Feb 26 | vsRangers | W1-0 | 32-14-8 | 72 PTS | PPG Paints Arena · Pittsburgh, PA |
| 55 | Sun Feb 27 | atJackets | W3-2 | 33-14-8 | 74 PTS | Nationwide Arena · Columbus, OH |
| 56 | Thu Mar 3 | atLightning | W5-1 | 34-14-8 | 76 PTS | AMALIE Arena · Tampa, FL |
| 57 | Fri Mar 4 | atHurricanes | L2-3 (OT) | 34-14-9 | 77 PTS | PNC Arena · Raleigh, NC |
| 58 | Tue Mar 8 | vsPanthers | L3-4 | 34-15-9 | 77 PTS | PPG Paints Arena · Pittsburgh, PA |
| 59 | Fri Mar 11 | vsKnights | W5-2 | 35-15-9 | 79 PTS | PPG Paints Arena · Pittsburgh, PA |
| 60 | Sun Mar 13 | vsHurricanes | W4-2 | 36-15-9 | 81 PTS | PPG Paints Arena · Pittsburgh, PA |
| 61 | Tue Mar 15 | atPredators | L1-4 | 36-16-9 | 81 PTS | Bridgestone Arena · Nashville, TN |
| 62 | Thu Mar 17 | atBlues | W3-2 (SO) | 37-16-9 | 83 PTS | Enterprise Center · St. Louis, MO |
| 63 | Sat Mar 19 | atCoyotes | W4-1 | 38-16-9 | 85 PTS | Mullett Arena · Tempe, AZ |
| 64 | Tue Mar 22 | vsJackets | W5-1 | 39-16-9 | 87 PTS | PPG Paints Arena · Pittsburgh, PA |
| 65 | Wed Mar 23 | atSabres | L3-4 (SO) | 39-16-10 | 88 PTS | KeyBank Center · Buffalo, NY |
| 66 | Fri Mar 25 | atRangers | L1-5 | 39-17-10 | 88 PTS | Madison Square Garden · Manhattan, NY |
| 67 | Sun Mar 27 | vsRed Wings | W11-2 | 40-17-10 | 90 PTS | PPG Paints Arena · Pittsburgh, PA |
| 68 | Tue Mar 29 | vsRangers | L2-3 | 40-18-10 | 90 PTS | PPG Paints Arena · Pittsburgh, PA |
| 69 | Thu Mar 31 | atWild | W4-3 (OT) | 41-18-10 | 92 PTS | Xcel Energy Center · St. Paul, MN |
| 70 | Sat Apr 2 | atAvalanche | L2-3 | 41-19-10 | 92 PTS | Ball Arena · Denver, CO |
| 71 | Tue Apr 5 | vsAvalanche | L4-6 | 41-20-10 | 92 PTS | PPG Paints Arena · Pittsburgh, PA |
| 72 | Thu Apr 7 | atRangers | L0-3 | 41-21-10 | 92 PTS | Madison Square Garden · Manhattan, NY |
| 73 | Sat Apr 9 | vsCapitals | L3-6 | 41-22-10 | 92 PTS | PPG Paints Arena · Pittsburgh, PA |
| 74 | Sun Apr 10 | vsPredators | W3-2 (OT) | 42-22-10 | 94 PTS | PPG Paints Arena · Pittsburgh, PA |
| 75 | Tue Apr 12 | atIslanders | L4-5 (SO) | 42-22-11 | 95 PTS | UBS Arena · Elmont, NY |
| 76 | Thu Apr 14 | vsIslanders | W6-3 | 43-22-11 | 97 PTS | PPG Paints Arena · Pittsburgh, PA |
| 77 | Sat Apr 16 | atBruins | L1-2 | 43-23-11 | 97 PTS | TD Garden · Boston, MA |
| 78 | Thu Apr 21 | vsBruins | W4-0 | 44-23-11 | 99 PTS | PPG Paints Arena · Pittsburgh, PA |
| 79 | Sat Apr 23 | atRed Wings | W7-2 | 45-23-11 | 101 PTS | Little Caesars Arena · Detroit, MI |
| 80 | Sun Apr 24 | atFlyers | L1-4 | 45-24-11 | 101 PTS | Wells Fargo Center · Philadelphia, PA |
| 81 | Tue Apr 26 | vsOilers | L1-5 | 45-25-11 | 101 PTS | PPG Paints Arena · Pittsburgh, PA |
| 82 | Fri Apr 29 | vsJackets | W5-3 | 46-25-11 | 103 PTS | PPG Paints Arena · Pittsburgh, PA |
| 1 | Tue May 3 | atRangers | W4-3 (OT) | 1-0 | 1.000 | Madison Square Garden · Manhattan, NY |
| 2 | Thu May 5 | atRangers | L2-5 | 1-1 | .500 | Madison Square Garden · Manhattan, NY |
| 3 | Sat May 7 | vsRangers | W7-4 | 2-1 | .667 | PPG Paints Arena · Pittsburgh, PA |
| 4 | Mon May 9 | vsRangers | W7-2 | 3-1 | .750 | PPG Paints Arena · Pittsburgh, PA |
| 5 | Wed May 11 | atRangers | L3-5 | 3-2 | .600 | Madison Square Garden · Manhattan, NY |
| 6 | Fri May 13 | vsRangers | L3-5 | 3-3 | .500 | PPG Paints Arena · Pittsburgh, PA |
| 7 | Sun May 15 | atRangers | L3-4 (OT) | 3-4 | .429 | Madison Square Garden · Manhattan, NY |
