The Colts had marched from their 16-yard line to the Miami 6 in just over two minutes when Manning was able to spike the ball to stop the clock with two seconds remaining.
The Colts had cut into the 18-point Miami lead on a touchdown pass from Manning to Marvin Harrison early in the fourth quarter and Mike Vanderjagt's 24-yard field goal with just under three minutes left.
The Dolphins, meanwhile, couldn't get on the scoreboard in the second half after a 21-point outburst in the first two quarters.
Running back Ricky Williams finished with 132 yards rushing and scored on a 10-yard touchdown catch to give the Dolphins their 21-3 lead late in the second quarter.
As they did against Detroit, the Dolphins scored on their first possession, marching 73 yards on nine plays. The score came when Jay Fiedler ran 1 yard on a naked bootleg.
The Dolphins made it 14-0 on their next possession after Derrick Rodgers came up with the first of three interceptions against Manning.
The 49-yard touchdown drive was capped by Fiedler's 9-yard pass to Rob Konrad on a third-and-3.
The Colts got on the board late in the first half when Vanderjagt hit a 25-yard field goal, but the Dolphins answered right back thanks in large part to Williams taking a screen pass 52 yards to the Colts 19-yard line.
After his touchdown made it 21-3, the Dolphins closed out a tremendous first half with Patrick Surtain's end zone interception.
Unfortunately, things weren't nearly as easy in the second half.
But the bottom line is that the Dolphins are now 2-0 with the hated Jets coming to town next Sunday.