| 26 | Fri Dec 12 | at Wizards | 7:00 PM | 3-19 | .136 | | Capital One Arena · Washington, D.C. |
| 27 | Sun Dec 14 | vs Hornets | 3:30 PM | 7-17 | .292 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| 28 | Wed Dec 17 | at Bulls | 8:00 PM | 9-14 | .391 | | United Center · Chicago, IL |
| 29 | Fri Dec 19 | vs Bulls | 7:30 PM | 9-14 | .391 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| 30 | Mon Dec 22 | vs Hornets | 7:00 PM | 7-17 | .292 | Peacock | Rocket Mortgage FieldHouse · Cleveland, OH |
| 31 | Tue Dec 23 | vs Pelicans | 7:30 PM | 3-22 | .120 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| 32 | Thu Dec 25 | at Knicks | 12:00 PM | 16-7 | .696 | ABC | Madison Square Garden · Manhattan, NY |
| 33 | Sat Dec 27 | at Rockets | 8:00 PM | 15-6 | .714 | | Toyota Center · Houston, TX |
| 34 | Mon Dec 29 | at Spurs | 8:00 PM | 16-7 | .696 | NBC | AT&T Center · San Antonio, TX |
| 35 | Wed Dec 31 | vs Suns | 3:30 PM | 14-10 | .583 | NBA TV | Rocket Mortgage FieldHouse · Cleveland, OH |
| 36 | Fri Jan 2 | vs Nuggets | 7:30 PM | 17-6 | .739 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| 37 | Sun Jan 4 | vs Pistons | 2:00 PM | 19-5 | .792 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| 38 | Tue Jan 6 | at Pacers | 7:00 PM | 6-18 | .250 | | Gainbridge Fieldhouse · Indianapolis, IN |
| 39 | Thu Jan 8 | at T-wolves | 8:00 PM | 15-9 | .625 | | Target Center · Minneapolis, MN |
| 40 | Sat Jan 10 | vs T-wolves | 1:00 PM | 15-9 | .625 | Amazon | Rocket Mortgage FieldHouse · Cleveland, OH |
| 41 | Mon Jan 12 | vs Jazz | 7:00 PM | 8-15 | .348 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| 42 | Wed Jan 14 | at 76ers | 7:00 PM | 13-10 | .565 | ESPN | Wells Fargo Center · Philadelphia, PA |
| 43 | Fri Jan 16 | at 76ers | 7:00 PM | 13-10 | .565 | | Wells Fargo Center · Philadelphia, PA |
| 44 | Mon Jan 19 | vs Thunder | 2:30 PM | 23-1 | .958 | NBC | Rocket Mortgage FieldHouse · Cleveland, OH |
| 45 | Wed Jan 21 | at Hornets | 7:00 PM | 7-17 | .292 | ESPN | Spectrum Center · Charlotte, NC |
| 46 | Fri Jan 23 | vs Kings | 7:30 PM | 6-18 | .250 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| 47 | Sat Jan 24 | at Magic | 7:00 PM | 14-10 | .583 | | Amway Center · Orlando, FL |
| 48 | Mon Jan 26 | vs Magic | 7:00 PM | 14-10 | .583 | Peacock | Rocket Mortgage FieldHouse · Cleveland, OH |
| 49 | Wed Jan 28 | vs Lakers | 7:00 PM | 17-6 | .739 | ESPN | Rocket Mortgage FieldHouse · Cleveland, OH |
| 50 | Fri Jan 30 | at Suns | 9:00 PM | 14-10 | .583 | | Footprint Center · Phoenix, AZ |
| 51 | Sun Feb 1 | at Blazers | 9:00 PM | 9-15 | .375 | | Moda Center · Portland, OR |
| 52 | Wed Feb 4 | at Clippers | 10:30 PM | 6-18 | .250 | | Intuit Dome · Inglewood, CA |
| 53 | Sat Feb 7 | at Kings | 10:00 PM | 6-18 | .250 | | Golden 1 Center · Sacramento, CA |
| 54 | Mon Feb 9 | at Nuggets | 9:00 PM | 17-6 | .739 | | Ball Arena · Denver, CO |
| 55 | Wed Feb 11 | vs Wizards | 7:00 PM | 3-19 | .136 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| --all-star break-- |
| 56 | Thu Feb 19 | vs Nets | 7:00 PM | 6-17 | .261 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| 57 | Fri Feb 20 | at Hornets | 7:00 PM | 7-17 | .292 | | Spectrum Center · Charlotte, NC |
| 58 | Sun Feb 22 | at Thunder | 1:00 PM | 23-1 | .958 | ABC | Paycom Center · Oklahoma City, OK |
| 59 | Tue Feb 24 | vs Knicks | 8:00 PM | 16-7 | .696 | NBC | Rocket Mortgage FieldHouse · Cleveland, OH |
| 60 | Wed Feb 25 | at Bucks | 8:00 PM | 10-15 | .400 | | Fiserv Forum · Milwaukee, WI |
| 61 | Fri Feb 27 | at Pistons | 7:00 PM | 19-5 | .792 | ESPN | Little Caesars Arena · Detroit, MI |
| 62 | Sun Mar 1 | at Nets | 3:30 PM | 6-17 | .261 | | Barclays Center · Brooklyn, NY |
| 63 | Tue Mar 3 | vs Pistons | 7:00 PM | 19-5 | .792 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| 64 | Sun Mar 8 | vs Celtics | 1:00 PM | 15-9 | .625 | ABC | Rocket Mortgage FieldHouse · Cleveland, OH |
| 65 | Mon Mar 9 | vs 76ers | 7:00 PM | 13-10 | .565 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| 66 | Wed Mar 11 | at Magic | 7:30 PM | 14-10 | .583 | ESPN | Amway Center · Orlando, FL |
| 67 | Fri Mar 13 | at Mavericks | 8:30 PM | 9-16 | .360 | | American Airlines Center · Dallas, TX |
| 68 | Sun Mar 15 | vs Mavericks | 3:30 PM | 9-16 | .360 | NBA TV | Rocket Mortgage FieldHouse · Cleveland, OH |
| 69 | Tue Mar 17 | at Bucks | 8:00 PM | 10-15 | .400 | NBC | Fiserv Forum · Milwaukee, WI |
| 70 | Thu Mar 19 | at Bulls | 8:00 PM | 9-14 | .391 | | United Center · Chicago, IL |
| 71 | Sat Mar 21 | at Pelicans | 7:00 PM | 3-22 | .120 | | Smoothie King Center · New Orleans, LA |
| 72 | Tue Mar 24 | vs Magic | 8:00 PM | 14-10 | .583 | NBC | Rocket Mortgage FieldHouse · Cleveland, OH |
| 73 | Wed Mar 25 | vs Heat | 7:30 PM | 14-10 | .583 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| 74 | Fri Mar 27 | vs Heat | 7:30 PM | 14-10 | .583 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| 75 | Mon Mar 30 | at Jazz | 9:00 PM | 8-15 | .348 | | Vivint Arena · Salt Lake City, UT |
| 76 | Tue Mar 31 | at Lakers | 10:30 PM | 17-6 | .739 | | Crypto.com Arena · Los Angeles, CA |
| 77 | Thu Apr 2 | at Warriors | 10:00 PM | 13-12 | .520 | Amazon | Chase Center · San Francisco, CA |
| 78 | Sun Apr 5 | vs Pacers | 6:00 PM | 6-18 | .250 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| 79 | Mon Apr 6 | at Grizzlies | 8:00 PM | 11-13 | .458 | | FedExForum · Memphis, TN |
| 80 | Wed Apr 8 | vs Hawks | 7:00 PM | 14-11 | .560 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| 81 | Fri Apr 10 | at Hawks | 7:30 PM | 14-11 | .560 | Amazon | State Farm Arena · Atlanta, GA |
| 82 | Sun Apr 12 | vs Wizards | 6:00 PM | 3-19 | .136 | | Rocket Mortgage FieldHouse · Cleveland, OH |