| 1 | Wed Oct 22 | at Mavericks | W125-92 | 1-0 | 1.000 | ESPN | American Airlines Center · Dallas, TX |
| 2 | Fri Oct 24 | at Pelicans | W120-116 (OT) | 2-0 | 1.000 | | Smoothie King Center · New Orleans, LA |
| 3 | Sun Oct 26 | vs Nets | W118-107 | 3-0 | 1.000 | | AT&T Center · San Antonio, TX |
| 4 | Mon Oct 27 | vs Raptors | W121-103 | 4-0 | 1.000 | | AT&T Center · San Antonio, TX |
| 5 | Thu Oct 30 | vs Heat | W107-101 | 5-0 | 1.000 | | AT&T Center · San Antonio, TX |
| 6 | Sun Nov 2 | at Suns | L118-130 | 5-1 | .833 | | Mortgage Matchup Center · Phoenix, AZ |
| 7 | Wed Nov 5 | at Lakers | L116-118 | 5-2 | .714 | ESPN | Crypto.com Arena · Los Angeles, CA |
| 8 | Fri Nov 7 | vs Rockets | W121-110 | 6-2 | .750 | Amazon | AT&T Center · San Antonio, TX |
| 9 | Sat Nov 8 | vs Pelicans | W126-119 | 7-2 | .778 | | AT&T Center · San Antonio, TX |
| 10 | Mon Nov 10 | at Bulls | W121-117 | 8-2 | .800 | | United Center · Chicago, IL |
| 11 | Wed Nov 12 | vs Warriors | L120-125 | 8-3 | .727 | | AT&T Center · San Antonio, TX |
| 12 | Fri Nov 14 | vs Warriors | L108-109 | 8-4 | .667 | Amazon | AT&T Center · San Antonio, TX |
| 13 | Sun Nov 16 | vs Kings | W123-110 | 9-4 | .692 | | AT&T Center · San Antonio, TX |
| 14 | Tue Nov 18 | vs Grizzlies | W111-101 | 10-4 | .714 | NBC | AT&T Center · San Antonio, TX |
| 15 | Thu Nov 20 | vs Hawks | W135-126 | 11-4 | .733 | NBA TV | AT&T Center · San Antonio, TX |
| 16 | Sun Nov 23 | at Suns | L102-111 | 11-5 | .688 | | Mortgage Matchup Center · Phoenix, AZ |
| 17 | Wed Nov 26 | at Blazers | W115-102 | 12-5 | .706 | | Moda Center · Portland, OR |
| 18 | Fri Nov 28 | at Nuggets | W139-136 | 13-5 | .722 | | Ball Arena · Denver, CO |
| 19 | Sun Nov 30 | at T-wolves | L112-125 | 13-6 | .684 | | Target Center · Minneapolis, MN |
| 20 | Tue Dec 2 | vs Grizzlies | W126-119 | 14-6 | .700 | | AT&T Center · San Antonio, TX |
| 21 | Wed Dec 3 | at Magic | W114-112 | 15-6 | .714 | | Kia Center · Orlando, FL |
| 22 | Fri Dec 5 | at Cavaliers | L117-130 | 15-7 | .682 | | Rocket Mortgage FieldHouse · Cleveland, OH |
| 23 | Mon Dec 8 | at Pelicans | W135-132 | 16-7 | .696 | | Smoothie King Center · New Orleans, LA |
| 24 | Wed Dec 10 | at Lakers | W132-119 | 17-7 | .708 | Amazon | Crypto.com Arena · Los Angeles, CA |
| 25 | Sat Dec 13 | at Thunder | W111-109 | 18-7 | .720 | Amazon | Paycom Center · Oklahoma City, OK |
| 26 | Tue Dec 16 | at Knicks | L113-124 | 0-1 | .000 | Amazon | Madison Square Garden · Manhattan, NY |
| 27 | Thu Dec 18 | vs Wizards | W119-94 | 19-7 | .731 | | AT&T Center · San Antonio, TX |
| 28 | Fri Dec 19 | at Hawks | W126-98 | 20-7 | .741 | | State Farm Arena · Atlanta, GA |
| 29 | Sun Dec 21 | at Wizards | W124-113 | 21-7 | .750 | | Capital One Arena · Washington, D.C. |
| 30 | Tue Dec 23 | vs Thunder | W130-110 | 22-7 | .759 | | AT&T Center · San Antonio, TX |
| 31 | Thu Dec 25 | at Thunder | W117-102 | 23-7 | .767 | ABC | Paycom Center · Oklahoma City, OK |
| 32 | Sat Dec 27 | vs Jazz | L114-127 | 23-8 | .742 | | AT&T Center · San Antonio, TX |
| 33 | Mon Dec 29 | vs Cavaliers | L101-113 | 23-9 | .719 | NBC | AT&T Center · San Antonio, TX |
| 34 | Wed Dec 31 | vs Knicks | W134-132 | 24-9 | .727 | NBA TV | AT&T Center · San Antonio, TX |
| 35 | Fri Jan 2 | at Pacers | W123-113 | 25-9 | .735 | | Gainbridge Fieldhouse · Indianapolis, IN |
| 36 | Sat Jan 3 | vs Blazers | L110-115 | 25-10 | .714 | | AT&T Center · San Antonio, TX |
| 37 | Tue Jan 6 | at Grizzlies | L105-106 | 25-11 | .694 | | FedExForum · Memphis, TN |
| 38 | Wed Jan 7 | vs Lakers | W107-91 | 26-11 | .703 | ESPN | AT&T Center · San Antonio, TX |
| 39 | Sat Jan 10 | at Celtics | W100-95 | 27-11 | .711 | | TD Garden · Boston, MA |
| 40 | Sun Jan 11 | at T-wolves | L103-104 | 27-12 | .692 | | Target Center · Minneapolis, MN |
| 41 | Tue Jan 13 | at Thunder | L98-119 | 27-13 | .675 | NBC | Paycom Center · Oklahoma City, OK |
| 42 | Thu Jan 15 | vs Bucks | W119-101 | 28-13 | .683 | | AT&T Center · San Antonio, TX |
| 43 | Sat Jan 17 | vs T-wolves | W126-123 | 29-13 | .690 | | AT&T Center · San Antonio, TX |
| 44 | Mon Jan 19 | vs Jazz | W123-110 | 30-13 | .698 | | AT&T Center · San Antonio, TX |
| 45 | Tue Jan 20 | at Rockets | L106-111 | 30-14 | .682 | NBC | Toyota Center · Houston, TX |
| 46 | Thu Jan 22 | at Jazz | W126-109 | 31-14 | .689 | | Vivint Arena · Salt Lake City, UT |
| 47 | Sun Jan 25 | vs Pelicans | L95-104 | 31-15 | .674 | | AT&T Center · San Antonio, TX |
| 48 | Wed Jan 28 | at Rockets | W111-99 | 32-15 | .681 | ESPN | Toyota Center · Houston, TX |
| 49 | Sat Jan 31 | at Hornets | L106-111 | 32-16 | .667 | Amazon | Spectrum Center · Charlotte, NC |
| 50 | Sun Feb 1 | vs Magic | W112-103 | 33-16 | .673 | | AT&T Center · San Antonio, TX |
| 51 | Wed Feb 4 | vs Thunder | W116-106 | 34-16 | .680 | ESPN | AT&T Center · San Antonio, TX |
| 52 | Thu Feb 5 | at Mavericks | W135-123 | 35-16 | .686 | | American Airlines Center · Dallas, TX |
| 53 | Sat Feb 7 | vs Mavericks | W138-125 | 36-16 | .692 | Amazon | AT&T Center · San Antonio, TX |