| 1 | Thu Oct 9 | vs Rangers | 7:00 PM | 39-36-7 | 85 PTS | KeyBank Center · Buffalo, NY |
| 2 | Sat Oct 11 | atBruins | 7:00 PM | 33-39-10 | 76 PTS | TD Garden · Boston, MA |
| 3 | Mon Oct 13 | vsAvalanche | 12:30 PM | 49-29-4 | 102 PTS | KeyBank Center · Buffalo, NY |
| 4 | Wed Oct 15 | vsSenators | 7:00 PM | 45-30-7 | 97 PTS | KeyBank Center · Buffalo, NY |
| 5 | Sat Oct 18 | vsPanthers | 1:00 PM | 47-31-4 | 98 PTS | KeyBank Center · Buffalo, NY |
| 6 | Mon Oct 20 | atCanadiens | 7:30 PM | 40-31-11 | 91 PTS | Bell Centre · Montreal, QC |
| 7 | Wed Oct 22 | vsRed Wings | 7:30 PM | 39-35-8 | 86 PTS | KeyBank Center · Buffalo, NY |
| 8 | Fri Oct 24 | vsMaple Leafs | 7:30 PM | 52-26-4 | 108 PTS | KeyBank Center · Buffalo, NY |
| 9 | Sat Oct 25 | atMaple Leafs | 7:00 PM | 52-26-4 | 108 PTS | Scotiabank Arena · Toronto, ON |
| 10 | Tue Oct 28 | vsJackets | 6:45 PM | 40-33-9 | 89 PTS | KeyBank Center · Buffalo, NY |
| 11 | Thu Oct 30 | atBruins | 7:00 PM | 33-39-10 | 76 PTS | TD Garden · Boston, MA |
| 12 | Sat Nov 1 | vsCapitals | 7:00 PM | 51-22-9 | 111 PTS | KeyBank Center · Buffalo, NY |
| 13 | Tue Nov 4 | vsMammoth | 7:00 PM | 0-0-0 | 0 PTS | KeyBank Center · Buffalo, NY |
| 14 | Thu Nov 6 | vsBlues | 7:00 PM | 44-30-8 | 96 PTS | KeyBank Center · Buffalo, NY |
| 15 | Sat Nov 8 | atHurricanes | 7:00 PM | 47-30-5 | 99 PTS | PNC Arena · Raleigh, NC |
| 16 | Wed Nov 12 | atMammoth | 9:00 PM | 0-0-0 | 0 PTS | Delta Center · Salt Lake City, UT |
| 17 | Thu Nov 13 | atAvalanche | 9:00 PM | 49-29-4 | 102 PTS | Ball Arena · Denver, CO |
| 18 | Sat Nov 15 | atRed Wings | 7:00 PM | 39-35-8 | 86 PTS | Little Caesars Arena · Detroit, MI |
| 19 | Mon Nov 17 | vsOilers | 7:00 PM | 48-29-5 | 101 PTS | KeyBank Center · Buffalo, NY |
| 20 | Wed Nov 19 | vsFlames | 7:30 PM | 41-27-14 | 96 PTS | KeyBank Center · Buffalo, NY |
| 21 | Fri Nov 21 | vsBlackhawks | 7:00 PM | 25-46-11 | 61 PTS | KeyBank Center · Buffalo, NY |
| 22 | Sun Nov 23 | vsHurricanes | 1:00 PM | 47-30-5 | 99 PTS | KeyBank Center · Buffalo, NY |
| 23 | Wed Nov 26 | atPenguins | 7:00 PM | 34-36-12 | 80 PTS | PPG Paints Arena · Pittsburgh, PA |
| 24 | Fri Nov 28 | vsDevils | 4:00 PM | 42-33-7 | 91 PTS | KeyBank Center · Buffalo, NY |
| 25 | Sat Nov 29 | atWild | 8:00 PM | 45-30-7 | 97 PTS | Xcel Energy Center · St. Paul, MN |
| 26 | Mon Dec 1 | vsJets | 7:30 PM | 56-22-4 | 116 PTS | KeyBank Center · Buffalo, NY |
| 27 | Wed Dec 3 | atFlyers | 7:30 PM | 33-39-10 | 76 PTS | Wells Fargo Center · Philadelphia, PA |
| 28 | Fri Dec 5 | atJets | 7:00 PM | 56-22-4 | 116 PTS | Canada Life Centre · Winnipeg, Manitoba |
| 29 | Mon Dec 8 | atFlames | 9:00 PM | 41-27-14 | 96 PTS | Scotiabank Saddledome · Calgary, Alberta |
| 30 | Tue Dec 9 | atOilers | 9:00 PM | 48-29-5 | 101 PTS | Rogers Place · Edmonton, AB |
| 31 | Thu Dec 11 | atCanucks | 10:00 PM | 38-30-14 | 90 PTS | Rogers Arena · Vancouver, British Columbia |
| 32 | Sun Dec 14 | atKraken | 8:00 PM | 35-41-6 | 76 PTS | Climate Pledge Arena · Seattle, WA |
| 33 | Thu Dec 18 | vsFlyers | 7:30 PM | 33-39-10 | 76 PTS | KeyBank Center · Buffalo, NY |
| 34 | Sat Dec 20 | vsIslanders | 5:00 PM | 35-35-12 | 82 PTS | KeyBank Center · Buffalo, NY |
| 35 | Sun Dec 21 | atDevils | 7:00 PM | 42-33-7 | 91 PTS | Prudential Center · Newark, NJ |
| 36 | Tue Dec 23 | atSenators | 7:00 PM | 45-30-7 | 97 PTS | Canadian Tire Centre · Ottawa, ON |
| 37 | Sat Dec 27 | vsBruins | 7:00 PM | 33-39-10 | 76 PTS | KeyBank Center · Buffalo, NY |
| 38 | Mon Dec 29 | atBlues | 8:00 PM | 44-30-8 | 96 PTS | Enterprise Center · St. Louis, MO |
| 39 | Wed Dec 31 | atStars | 8:00 PM | 50-26-6 | 106 PTS | American Airlines Center · Dallas, TX |
| 40 | Sat Jan 3 | atJackets | 3:00 PM | 40-33-9 | 89 PTS | Nationwide Arena · Columbus, OH |
| 41 | Tue Jan 6 | vsCanucks | 7:00 PM | 38-30-14 | 90 PTS | KeyBank Center · Buffalo, NY |
| 42 | Thu Jan 8 | atRangers | 7:00 PM | 39-36-7 | 85 PTS | Madison Square Garden · Manhattan, NY |
| 43 | Sat Jan 10 | vsDucks | 7:00 PM | 35-37-10 | 80 PTS | KeyBank Center · Buffalo, NY |
| 44 | Mon Jan 12 | vsPanthers | 7:00 PM | 47-31-4 | 98 PTS | KeyBank Center · Buffalo, NY |
| 45 | Wed Jan 14 | vsFlyers | 7:30 PM | 33-39-10 | 76 PTS | KeyBank Center · Buffalo, NY |
| 46 | Thu Jan 15 | vsCanadiens | 7:00 PM | 40-31-11 | 91 PTS | KeyBank Center · Buffalo, NY |
| 47 | Sat Jan 17 | vsWild | 12:30 PM | 45-30-7 | 97 PTS | KeyBank Center · Buffalo, NY |
| 48 | Mon Jan 19 | atHurricanes | 1:30 PM | 47-30-5 | 99 PTS | PNC Arena · Raleigh, NC |
| 49 | Tue Jan 20 | atPredators | 8:00 PM | 30-44-8 | 68 PTS | Bridgestone Arena · Nashville, TN |
| 50 | Thu Jan 22 | atCanadiens | 7:00 PM | 40-31-11 | 91 PTS | Bell Centre · Montreal, QC |
| 51 | Sat Jan 24 | atIslanders | 1:00 PM | 35-35-12 | 82 PTS | UBS Arena · Elmont, NY |
| 52 | Tue Jan 27 | atMaple Leafs | 7:00 PM | 52-26-4 | 108 PTS | Scotiabank Arena · Toronto, ON |
| 53 | Thu Jan 29 | vsKings | 7:00 PM | 48-25-9 | 105 PTS | KeyBank Center · Buffalo, NY |
| 54 | Sat Jan 31 | vsCanadiens | 7:00 PM | 40-31-11 | 91 PTS | KeyBank Center · Buffalo, NY |
| 55 | Mon Feb 2 | atPanthers | 7:00 PM | 47-31-4 | 98 PTS | Amerant Bank Arena · Sunrise, FL |
| 56 | Tue Feb 3 | atLightning | 7:30 PM | 47-27-8 | 102 PTS | AMALIE Arena · Tampa, FL |
| 57 | Thu Feb 5 | vsPenguins | 7:00 PM | 34-36-12 | 80 PTS | KeyBank Center · Buffalo, NY |
| 58 | Wed Feb 25 | atDevils | 7:00 PM | 42-33-7 | 91 PTS | Prudential Center · Newark, NJ |
| 59 | Fri Feb 27 | atPanthers | 7:00 PM | 47-31-4 | 98 PTS | Amerant Bank Arena · Sunrise, FL |
| 60 | Sat Feb 28 | atLightning | 7:00 PM | 47-27-8 | 102 PTS | AMALIE Arena · Tampa, FL |
| 61 | Tue Mar 3 | vsKnights | 7:00 PM | 50-22-10 | 110 PTS | KeyBank Center · Buffalo, NY |
| 62 | Thu Mar 5 | atPenguins | 7:00 PM | 34-36-12 | 80 PTS | PPG Paints Arena · Pittsburgh, PA |
| 63 | Sat Mar 7 | vsPredators | 5:30 PM | 30-44-8 | 68 PTS | KeyBank Center · Buffalo, NY |
| 64 | Sun Mar 8 | vsLightning | 6:00 PM | 47-27-8 | 102 PTS | KeyBank Center · Buffalo, NY |
| 65 | Tue Mar 10 | vsSharks | 7:00 PM | 20-50-12 | 52 PTS | KeyBank Center · Buffalo, NY |
| 66 | Thu Mar 12 | vsCapitals | 7:00 PM | 51-22-9 | 111 PTS | KeyBank Center · Buffalo, NY |
| 67 | Sat Mar 14 | vsMaple Leafs | 7:00 PM | 52-26-4 | 108 PTS | KeyBank Center · Buffalo, NY |
| 68 | Tue Mar 17 | atKnights | 10:00 PM | 50-22-10 | 110 PTS | T-Mobile Arena · Las Vegas, NV |
| 69 | Thu Mar 19 | atSharks | 10:00 PM | 20-50-12 | 52 PTS | SAP Center · San Jose, CA |
| 70 | Sat Mar 21 | atKings | 4:00 PM | 48-25-9 | 105 PTS | Crypto.com Arena · Los Angeles, CA |
| 71 | Sun Mar 22 | atDucks | 8:00 PM | 35-37-10 | 80 PTS | Honda Center · Anaheim, CA |
| 72 | Wed Mar 25 | vsBruins | 7:00 PM | 33-39-10 | 76 PTS | KeyBank Center · Buffalo, NY |
| 73 | Fri Mar 27 | vsRed Wings | 7:00 PM | 39-35-8 | 86 PTS | KeyBank Center · Buffalo, NY |
| 74 | Sat Mar 28 | vsKraken | 5:30 PM | 35-41-6 | 76 PTS | KeyBank Center · Buffalo, NY |
| 75 | Tue Mar 31 | vsIslanders | 7:00 PM | 35-35-12 | 82 PTS | KeyBank Center · Buffalo, NY |
| 76 | Thu Apr 2 | atSenators | 7:00 PM | 45-30-7 | 97 PTS | Canadian Tire Centre · Ottawa, ON |
| 77 | Sat Apr 4 | atCapitals | 7:00 PM | 51-22-9 | 111 PTS | Capital One Arena · Washington, D.C. |
| 78 | Mon Apr 6 | vsLightning | 7:00 PM | 47-27-8 | 102 PTS | KeyBank Center · Buffalo, NY |
| 79 | Wed Apr 8 | atRangers | 7:00 PM | 39-36-7 | 85 PTS | Madison Square Garden · Manhattan, NY |
| 80 | Thu Apr 9 | vsJackets | 7:00 PM | 40-33-9 | 89 PTS | KeyBank Center · Buffalo, NY |
| 81 | Mon Apr 13 | atBlackhawks | 8:30 PM | 25-46-11 | 61 PTS | United Center · Chicago, IL |
| 82 | Wed Apr 15 | vsStars | 7:00 PM | 50-26-6 | 106 PTS | KeyBank Center · Buffalo, NY |
