| 1 | Thu Oct 9 | vs Rangers | L0-4 | 0-1-0 | 0 PTS | KeyBank Center · Buffalo, NY |
| 2 | Sat Oct 11 | atBruins | L1-3 | 0-2-0 | 0 PTS | TD Garden · Boston, MA |
| 3 | Mon Oct 13 | vsAvalanche | L1-3 | 0-3-0 | 0 PTS | KeyBank Center · Buffalo, NY |
| 4 | Wed Oct 15 | vsSenators | W8-4 | 1-3-0 | 2 PTS | KeyBank Center · Buffalo, NY |
| 5 | Sat Oct 18 | vsPanthers | W3-0 | 2-3-0 | 4 PTS | KeyBank Center · Buffalo, NY |
| 6 | Mon Oct 20 | atCanadiens | L2-4 | 2-4-0 | 4 PTS | Bell Centre · Montreal, QC |
| 7 | Wed Oct 22 | vsRed Wings | W4-2 | 3-4-0 | 6 PTS | KeyBank Center · Buffalo, NY |
| 8 | Fri Oct 24 | vsMaple Leafs | W5-3 | 4-4-0 | 8 PTS | KeyBank Center · Buffalo, NY |
| 9 | Sat Oct 25 | atMaple Leafs | L3-4 (OT) | 4-4-1 | 9 PTS | Scotiabank Arena · Toronto, ON |
| 10 | Tue Oct 28 | vsJackets | L3-4 (OT) | 4-4-2 | 10 PTS | KeyBank Center · Buffalo, NY |
| 11 | Thu Oct 30 | atBruins | L3-4 (OT) | 4-4-3 | 11 PTS | TD Garden · Boston, MA |
| 12 | Sat Nov 1 | vsCapitals | W4-3 (SO) | 5-4-3 | 13 PTS | KeyBank Center · Buffalo, NY |
| 13 | Tue Nov 4 | vsMammoth | L1-2 (OT) | 5-4-4 | 14 PTS | KeyBank Center · Buffalo, NY |
| 14 | Thu Nov 6 | vsBlues | L0-3 | 5-5-4 | 14 PTS | KeyBank Center · Buffalo, NY |
| 15 | Sat Nov 8 | atHurricanes | L3-6 | 5-6-4 | 14 PTS | PNC Arena · Raleigh, NC |
| 16 | Wed Nov 12 | atMammoth | L2-5 | 5-7-4 | 14 PTS | Delta Center · Salt Lake City, UT |
| 17 | Thu Nov 13 | atAvalanche | L3-6 | 5-8-4 | 14 PTS | Ball Arena · Denver, CO |
| 18 | Sat Nov 15 | atRed Wings | W5-4 (OT) | 6-8-4 | 16 PTS | Little Caesars Arena · Detroit, MI |
| 19 | Mon Nov 17 | vsOilers | W5-1 | 7-8-4 | 18 PTS | KeyBank Center · Buffalo, NY |
| 20 | Wed Nov 19 | vsFlames | L2-6 | 7-9-4 | 18 PTS | KeyBank Center · Buffalo, NY |
| 21 | Fri Nov 21 | vsBlackhawks | W9-3 | 8-9-4 | 20 PTS | KeyBank Center · Buffalo, NY |
| 22 | Sun Nov 23 | vsHurricanes | W4-1 | 9-9-4 | 22 PTS | KeyBank Center · Buffalo, NY |
| 23 | Wed Nov 26 | atPenguins | L2-4 | 9-10-4 | 22 PTS | PPG Paints Arena · Pittsburgh, PA |
| 24 | Fri Nov 28 | vsDevils | L0-5 | 9-11-4 | 22 PTS | KeyBank Center · Buffalo, NY |
| 25 | Sat Nov 29 | atWild | W3-2 (SO) | 10-11-4 | 24 PTS | Xcel Energy Center · St. Paul, MN |
| 26 | Mon Dec 1 | vsJets | W5-1 | 11-11-4 | 26 PTS | KeyBank Center · Buffalo, NY |
| 27 | Wed Dec 3 | atFlyers | L2-5 | 11-12-4 | 26 PTS | Wells Fargo Center · Philadelphia, PA |
| 28 | Fri Dec 5 | atJets | L1-4 | 11-13-4 | 26 PTS | Canada Life Centre · Winnipeg, Manitoba |
| 29 | Mon Dec 8 | atFlames | L4-7 | 11-14-4 | 26 PTS | Scotiabank Saddledome · Calgary, Alberta |
| 30 | Tue Dec 9 | atOilers | W4-3 (OT) | 12-14-4 | 28 PTS | Rogers Place · Edmonton, AB |
| 31 | Thu Dec 11 | atCanucks | W3-2 | 13-14-4 | 30 PTS | Rogers Arena · Vancouver, British Columbia |
| 32 | Sun Dec 14 | atKraken | W3-1 | 14-14-4 | 32 PTS | Climate Pledge Arena · Seattle, WA |
| 33 | Thu Dec 18 | vsFlyers | W5-3 | 15-14-4 | 34 PTS | KeyBank Center · Buffalo, NY |
| 34 | Sat Dec 20 | vsIslanders | W3-2 (SO) | 16-14-4 | 36 PTS | KeyBank Center · Buffalo, NY |
| 35 | Sun Dec 21 | atDevils | W3-1 | 17-14-4 | 38 PTS | Prudential Center · Newark, NJ |
| 36 | Tue Dec 23 | atSenators | W3-2 (OT) | 18-14-4 | 40 PTS | Canadian Tire Centre · Ottawa, ON |
| 37 | Sat Dec 27 | vsBruins | W4-1 | 19-14-4 | 42 PTS | KeyBank Center · Buffalo, NY |
| 38 | Mon Dec 29 | atBlues | W4-2 | 20-14-4 | 44 PTS | Enterprise Center · St. Louis, MO |
| 39 | Wed Dec 31 | atStars | W4-1 | 21-14-4 | 46 PTS | American Airlines Center · Dallas, TX |
| 40 | Sat Jan 3 | atJackets | L1-5 | 21-15-4 | 46 PTS | Nationwide Arena · Columbus, OH |
| 41 | Tue Jan 6 | vsCanucks | W5-3 | 22-15-4 | 48 PTS | KeyBank Center · Buffalo, NY |
| 42 | Thu Jan 8 | atRangers | W5-2 | 23-15-4 | 50 PTS | Madison Square Garden · Manhattan, NY |
| 43 | Sat Jan 10 | vsDucks | W5-3 | 24-15-4 | 52 PTS | KeyBank Center · Buffalo, NY |
| 44 | Mon Jan 12 | vsPanthers | L3-4 | 24-16-4 | 52 PTS | KeyBank Center · Buffalo, NY |
| 45 | Wed Jan 14 | vsFlyers | W5-2 | 25-16-4 | 54 PTS | KeyBank Center · Buffalo, NY |
| 46 | Thu Jan 15 | vsCanadiens | W5-3 | 26-16-4 | 56 PTS | KeyBank Center · Buffalo, NY |
| 47 | Sat Jan 17 | vsWild | L4-5 (OT) | 26-16-5 | 57 PTS | KeyBank Center · Buffalo, NY |
| 48 | Mon Jan 19 | atHurricanes | L1-2 | 26-17-5 | 57 PTS | PNC Arena · Raleigh, NC |
| 49 | Tue Jan 20 | atPredators | W5-3 | 27-17-5 | 59 PTS | Bridgestone Arena · Nashville, TN |
| 50 | Thu Jan 22 | atCanadiens | W4-2 | 28-17-5 | 61 PTS | Bell Centre · Montreal, QC |
| 51 | Sat Jan 24 | atIslanders | W5-0 | 29-17-5 | 63 PTS | UBS Arena · Elmont, NY |
| 52 | Tue Jan 27 | atMaple Leafs | W7-4 | 30-17-5 | 65 PTS | Scotiabank Arena · Toronto, ON |
| 53 | Thu Jan 29 | vsKings | W4-1 | 31-17-5 | 67 PTS | KeyBank Center · Buffalo, NY |
| 54 | Sat Jan 31 | vsCanadiens | L2-4 | 31-18-5 | 67 PTS | KeyBank Center · Buffalo, NY |
| 55 | Mon Feb 2 | atPanthers | W5-3 | 32-18-5 | 69 PTS | Amerant Bank Arena · Sunrise, FL |
| 56 | Tue Feb 3 | atLightning | L3-4 (OT) | 32-18-6 | 70 PTS | Benchmark International Arena · Tampa, FL |
| 57 | Thu Feb 5 | vsPenguins | L2-5 | 32-19-6 | 70 PTS | KeyBank Center · Buffalo, NY |
| 58 | Wed Feb 25 | atDevils | W2-1 | 33-19-6 | 72 PTS | Prudential Center · Newark, NJ |
| 59 | Fri Feb 27 | atPanthers | W3-2 | 34-19-6 | 74 PTS | Amerant Bank Arena · Sunrise, FL |
| 60 | Sat Feb 28 | atLightning | W6-2 | 35-19-6 | 76 PTS | Benchmark International Arena · Tampa, FL |
