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