Vinatieri kicked four field goals, including a 51-yarder with 1:38 remaining in overtime to give the Colts a 26-23 victory over the San Francisco 49ers in Lucas Oil Stadium.
Colts running back Marlon Mack, who ran 22 yards for a third-quarter touchdown, ran 35 yards to the San Francisco 34-yard line to set up Vinatieri's game-winning field goal.
With the victory, Indianapolis (2-3) avoided being swept by the NFC West. The Los Angeles Rams, Arizona and Seattle defeated the Colts during the season's first four weeks by a combined 108-40 score.
"We kind of set a line at 55 yards, and if the situation is right, you take it," Vinatieri said of his winning kick. "You sure try to be ready for that situation. The guys up front did a fantastic job, as did the snapper and the holder. It makes my job a little easier, and I appreciate all the hard work they put in.
"These (game-winners) never get old. The thing is they all are different. I am not against the 22-yarders that win a game. I will take them any way I can get them. I didn't feel much wind today (from open window at stadium's north end). The lines of demarcation were about the same on all four. On the game-winner, the ball started a little right, but my ball usually draws a couple of yards to the left."
The kick left San Francisco (0-5) as one of three remaining winless teams in the NFL.
"We had opportunities there and we didn't get it done again," 49ers head coach Kyle Shanahan said. "Saying the same things I said the past few weeks. Nothing you can do but go back to work and get better."
The Colts' victory came on the day the organization inducted Super Bowl-winning quarterback Peyton Manning into their Ring of Honor.
Indianapolis quarterback Jacoby Brissett finished 22-of-34 passing for 314 yards and one interception. 49ers quarterback Brian Hoyer completed 29 of 46 passes for 353 yards and two touchdowns. Wide receiver T.Y. Hilton caught seven passes for 177 yards for the Colts.
Colts running back Frank Gore, a former San Francisco star, had 48 yards on 14 carries and moved past Eric Dickerson (13,259 from 1983-93) for seventh place on the all-time career rushing yardage list. Gore's total is 13,304.
The Colts built a sizable lead in regulation time.
"We make it harder for ourselves sometimes than it has to be," Indianapolis head coach Chuck Pagano said. "We worked our tails off, and it was a heck of a ball game. At the end, Vinatieri showed why he is a sure first (ballot Hall of Famer). He is unbelievable, and we got a lot of great plays from a lot of different guys.
"We had a chance to close it out, but the 49ers did a heck of a job. We found a way in overtime. We had chances to close it out. When you are up 14 in the fourth quarter, you should get it done, but San Francisco found ways to get back in it. We just found a way to make a few more plays than they did."
Brissett capped a six-play, 75-yard drive with 9:56 remaining, extending the Indianapolis lead to 23-9, using a 63-yard pass to Hilton and a 16-yard Mack run to the 49ers' 1-yard line as the catalyst.
San Francisco cut the deficit to 23-16 with eight minutes to go on Hoyer's 6-yard touchdown pass to fullback Kyle Juszczyk, capping a five-play, 79-yard drive.
The 49ers pulled even at 23 with 20 seconds remaining on Hoyer's fourth-down, 5-yard touchdown pass to tight end George Kittle, capping a 14-play, 89-yard drive.
While the 49ers primarily did their offensive damage through the air, Shanahan was pleased with backup running back Matt Breida, who rushed 10 times for 49 yards. Starter Carlos Hyde rushed eight times for 11 yards.
"Breida got more work today because he was hot," Shanahan said. "We wanted to go with the hot hand."
Vinatieri also kicked field goals of 52, 23 and 38 yards, helping the Colts build a 14-point, fourth-quarter lead. Those kicks capped drives of 41, 72 and 30 yards.
The 49ers got field goals of 28, 43 and 40 yards from Robbie Gould, who became the 31st player in NFL history to make at least 300.
NOTES: The Colts lost MLB Anthony Walker with a hamstring injury ... San Francisco WR Marquise Goodwin caught five passes for a career-high 116 yards. ... Indianapolis entered Sunday's game ranked 25th in scoring at 17.8 points, and the 49ers entered ranked 26th at 16.5 ... The Colts improved to 2-1 at home, also defeating Cleveland in Lucas Oil.