Indianapolis Colts versus San Francisco 49ers Head-to-head history

Dec 22, 2025	Score	Moneyline	Spread	Game total
San Francisco 49ersSF	48	-220 W	-4.25 (-110) W	O 46.5 (-110) W U 46.5 (-110) L
Indianapolis ColtsIND	27	+185 L	+4.25 (-110) L

San Francisco 49ers defeated Indianapolis Colts 48-27

San Francisco 49ers defeated Indianapolis Colts 48-27 on December 22, 2025, a 21-point decision in the series. San Francisco 49ers' strongest period was the 1st quarter, when it outscored its opponent 14-7. Against SportsJaw's recorded San Francisco 49ers -4.25 (-110) spread, San Francisco 49ers covered, while the 75 combined points finished over the recorded total of 46.5.