| 1 | Thu Oct 13 | vs Senators | W4-1 | 1-0-0 | 2 PTS | KeyBank Center · Buffalo, NY |
| 2 | Sat Oct 15 | vsPanthers | L3-4 | 1-1-0 | 2 PTS | KeyBank Center · Buffalo, NY |
| 3 | Tue Oct 18 | atOilers | W4-2 | 2-1-0 | 4 PTS | Rogers Place · Edmonton, AB |
| 4 | Thu Oct 20 | atFlames | W6-3 | 3-1-0 | 6 PTS | Scotiabank Saddledome · Calgary, Alberta |
| 5 | Sat Oct 22 | atCanucks | W5-1 | 4-1-0 | 8 PTS | Rogers Arena · Vancouver, British Columbia |
| 6 | Tue Oct 25 | atKraken | L1-5 | 4-2-0 | 8 PTS | Climate Pledge Arena · Seattle, WA |
| 7 | Thu Oct 27 | vsCanadiens | L2-3 | 4-3-0 | 8 PTS | KeyBank Center · Buffalo, NY |
| 8 | Sat Oct 29 | vsBlackhawks | W4-3 (OT) | 5-3-0 | 10 PTS | KeyBank Center · Buffalo, NY |
| 9 | Mon Oct 31 | vsRed Wings | W8-3 | 6-3-0 | 12 PTS | KeyBank Center · Buffalo, NY |
| 10 | Wed Nov 2 | vsPenguins | W6-3 | 7-3-0 | 14 PTS | KeyBank Center · Buffalo, NY |
| 11 | Fri Nov 4 | atHurricanes | L3-5 | 7-4-0 | 14 PTS | PNC Arena · Raleigh, NC |
| 12 | Sat Nov 5 | atLightning | L3-5 | 7-5-0 | 14 PTS | AMALIE Arena · Tampa, FL |
| 13 | Tue Nov 8 | vsCoyotes | L1-4 | 7-6-0 | 14 PTS | KeyBank Center · Buffalo, NY |
| 14 | Thu Nov 10 | vsKnights | L4-7 | 7-7-0 | 14 PTS | KeyBank Center · Buffalo, NY |
| 15 | Sat Nov 12 | vsBruins | L1-3 | 7-8-0 | 14 PTS | KeyBank Center · Buffalo, NY |
| 16 | Tue Nov 15 | vsCanucks | L4-5 | 7-9-0 | 14 PTS | KeyBank Center · Buffalo, NY |
| 17 | Wed Nov 16 | atSenators | L1-4 | 7-10-0 | 14 PTS | Canadian Tire Centre · Ottawa, ON |
| 18 | Sat Nov 19 | atMaple Leafs | L2-5 | 7-11-0 | 14 PTS | Scotiabank Arena · Toronto, ON |
| 19 | Tue Nov 22 | atCanadiens | W7-2 | 8-11-0 | 16 PTS | Bell Centre · Montreal, QC |
| 20 | Wed Nov 23 | vsBlues | W6-2 | 9-11-0 | 18 PTS | KeyBank Center · Buffalo, NY |
| 21 | Fri Nov 25 | vsDevils | L1-3 | 9-12-0 | 18 PTS | KeyBank Center · Buffalo, NY |
| 22 | Mon Nov 28 | vsLightning | L5-6 (OT) | 9-12-1 | 19 PTS | KeyBank Center · Buffalo, NY |
| 23 | Wed Nov 30 | atRed Wings | W5-4 (SO) | 10-12-1 | 21 PTS | Little Caesars Arena · Detroit, MI |
| 24 | Thu Dec 1 | vsAvalanche | L4-6 | 10-13-1 | 21 PTS | KeyBank Center · Buffalo, NY |
| 25 | Sun Dec 4 | vsSharks | W6-3 | 11-13-1 | 23 PTS | KeyBank Center · Buffalo, NY |
| 26 | Wed Dec 7 | atJackets | W9-4 | 12-13-1 | 25 PTS | Nationwide Arena · Columbus, OH |
| 27 | Fri Dec 9 | vsPenguins | L3-4 (OT) | 12-13-2 | 26 PTS | KeyBank Center · Buffalo, NY |
| 28 | Sat Dec 10 | atPenguins | L1-3 | 12-14-2 | 26 PTS | PPG Paints Arena · Pittsburgh, PA |
| 29 | Tue Dec 13 | vsKings | W6-0 | 13-14-2 | 28 PTS | KeyBank Center · Buffalo, NY |
| 30 | Thu Dec 15 | atAvalanche | W4-2 | 14-14-2 | 30 PTS | Ball Arena · Denver, CO |
| 31 | Sat Dec 17 | atCoyotes | W5-2 | 15-14-2 | 32 PTS | Mullett Arena · Tempe, AZ |
| 32 | Mon Dec 19 | atKnights | W3-2 | 16-14-2 | 34 PTS | T-Mobile Arena · Las Vegas, NV |
| 33 | Thu Dec 29 | vsRed Wings | W6-3 | 17-14-2 | 36 PTS | KeyBank Center · Buffalo, NY |
| 34 | Sat Dec 31 | atBruins | W4-3 (OT) | 18-14-2 | 38 PTS | TD Garden · Boston, MA |
| 35 | Sun Jan 1 | atSenators | L1-3 | 18-15-2 | 38 PTS | Canadian Tire Centre · Ottawa, ON |
| 36 | Tue Jan 3 | atCapitals | W5-4 (OT) | 19-15-2 | 40 PTS | Capital One Arena · Washington, D.C. |
| 37 | Sat Jan 7 | vsWild | W6-5 (OT) | 20-15-2 | 42 PTS | KeyBank Center · Buffalo, NY |
| 38 | Mon Jan 9 | vsFlyers | L0-4 | 20-16-2 | 42 PTS | KeyBank Center · Buffalo, NY |
| 39 | Tue Jan 10 | vsKraken | L3-4 | 20-17-2 | 42 PTS | KeyBank Center · Buffalo, NY |
| 40 | Thu Jan 12 | vsJets | L2-4 | 20-18-2 | 42 PTS | KeyBank Center · Buffalo, NY |
| 41 | Sat Jan 14 | atPredators | W5-3 | 21-18-2 | 44 PTS | Bridgestone Arena · Nashville, TN |
| 42 | Mon Jan 16 | vsPanthers | L1-4 | 21-19-2 | 44 PTS | KeyBank Center · Buffalo, NY |
| 43 | Tue Jan 17 | atBlackhawks | L3-4 (OT) | 21-19-3 | 45 PTS | United Center · Chicago, IL |
| 44 | Thu Jan 19 | vsIslanders | W3-2 (OT) | 22-19-3 | 47 PTS | KeyBank Center · Buffalo, NY |
| 45 | Sat Jan 21 | vsDucks | W6-3 | 23-19-3 | 49 PTS | KeyBank Center · Buffalo, NY |
| 46 | Mon Jan 23 | atStars | W3-2 (OT) | 24-19-3 | 51 PTS | American Airlines Center · Dallas, TX |
| 47 | Tue Jan 24 | atBlues | W5-3 | 25-19-3 | 53 PTS | Enterprise Center · St. Louis, MO |
| 48 | Thu Jan 26 | atJets | W3-2 | 26-19-3 | 55 PTS | Canada Life Centre · Winnipeg, Manitoba |
| 49 | Sat Jan 28 | atWild | L2-3 (SO) | 26-19-4 | 56 PTS | Xcel Energy Center · St. Paul, MN |
| 50 | Wed Feb 1 | vsHurricanes | L1-5 | 26-20-4 | 56 PTS | KeyBank Center · Buffalo, NY |
| 51 | Sat Feb 11 | vsFlames | L2-7 | 26-21-4 | 56 PTS | KeyBank Center · Buffalo, NY |
| 52 | Mon Feb 13 | atKings | L2-5 | 26-22-4 | 56 PTS | Crypto.com Arena · Los Angeles, CA |
| 53 | Wed Feb 15 | atDucks | W7-3 | 27-22-4 | 58 PTS | Honda Center · Anaheim, CA |
| 54 | Sat Feb 18 | atSharks | W4-2 | 28-22-4 | 60 PTS | SAP Center · San Jose, CA |
| 55 | Tue Feb 21 | vsMaple Leafs | L3-6 | 28-23-4 | 60 PTS | KeyBank Center · Buffalo, NY |
| 56 | Thu Feb 23 | atLightning | W6-5 (OT) | 29-23-4 | 62 PTS | AMALIE Arena · Tampa, FL |
| 57 | Fri Feb 24 | atPanthers | W3-1 | 30-23-4 | 64 PTS | Amerant Bank Arena · Sunrise, FL |
| 58 | Sun Feb 26 | vsCapitals | W7-4 | 31-23-4 | 66 PTS | KeyBank Center · Buffalo, NY |
| 59 | Tue Feb 28 | vsJackets | L3-5 | 31-24-4 | 66 PTS | KeyBank Center · Buffalo, NY |
| 60 | Thu Mar 2 | atBruins | L1-7 | 31-25-4 | 66 PTS | TD Garden · Boston, MA |
| 61 | Sat Mar 4 | vsLightning | W5-3 | 32-25-4 | 68 PTS | KeyBank Center · Buffalo, NY |
| 62 | Mon Mar 6 | vsOilers | L2-3 | 32-26-4 | 68 PTS | KeyBank Center · Buffalo, NY |
| 63 | Tue Mar 7 | atIslanders | L2-3 | 32-27-4 | 68 PTS | UBS Arena · Elmont, NY |
| 64 | Thu Mar 9 | vsStars | L4-10 | 32-28-4 | 68 PTS | KeyBank Center · Buffalo, NY |
| 65 | Sat Mar 11 | vsRangers | L1-2 (OT) | 32-28-5 | 69 PTS | KeyBank Center · Buffalo, NY |
| 66 | Mon Mar 13 | atMaple Leafs | W4-3 | 33-28-5 | 71 PTS | Scotiabank Arena · Toronto, ON |
| 67 | Wed Mar 15 | atCapitals | L4-5 (SO) | 33-28-6 | 72 PTS | Capital One Arena · Washington, D.C. |
| 68 | Fri Mar 17 | atFlyers | L2-5 | 33-29-6 | 72 PTS | Wells Fargo Center · Philadelphia, PA |
| 69 | Sun Mar 19 | vsBruins | L0-7 | 33-30-6 | 72 PTS | KeyBank Center · Buffalo, NY |
| 70 | Tue Mar 21 | vsPredators | L3-7 | 33-31-6 | 72 PTS | KeyBank Center · Buffalo, NY |
| 71 | Fri Mar 24 | vsDevils | W5-4 | 34-31-6 | 74 PTS | KeyBank Center · Buffalo, NY |
| 72 | Sat Mar 25 | atIslanders | W2-0 | 35-31-6 | 76 PTS | UBS Arena · Elmont, NY |
| 73 | Mon Mar 27 | vsCanadiens | L3-4 (SO) | 35-31-7 | 77 PTS | KeyBank Center · Buffalo, NY |
| 74 | Fri Mar 31 | vsRangers | W3-2 (OT) | 36-31-7 | 79 PTS | KeyBank Center · Buffalo, NY |
| 75 | Sat Apr 1 | atFlyers | W6-3 | 37-31-7 | 81 PTS | Wells Fargo Center · Philadelphia, PA |
| 76 | Tue Apr 4 | atPanthers | L1-2 | 37-32-7 | 81 PTS | Amerant Bank Arena · Sunrise, FL |
| 77 | Thu Apr 6 | atRed Wings | W7-6 (SO) | 38-32-7 | 83 PTS | Little Caesars Arena · Detroit, MI |
| 78 | Sat Apr 8 | vsHurricanes | W4-3 | 39-32-7 | 85 PTS | KeyBank Center · Buffalo, NY |
| 79 | Mon Apr 10 | atRangers | W3-2 (SO) | 40-32-7 | 87 PTS | Madison Square Garden · Manhattan, NY |
| 80 | Tue Apr 11 | atDevils | L2-6 | 40-33-7 | 87 PTS | Prudential Center · Newark, NJ |
| 81 | Thu Apr 13 | vsSenators | W4-3 (OT) | 41-33-7 | 89 PTS | KeyBank Center · Buffalo, NY |
| 82 | Fri Apr 14 | atJackets | W5-2 | 42-33-7 | 91 PTS | Nationwide Arena · Columbus, OH |
