"You can't end up relying on that, falling back on it," coach Tony Dungy said. "We've just got to play better and I think we will."
Manning used an unorthodox strategy, scoring twice on touchdown runs, to beat Jacksonville and the New York Jets the previous two weeks.
Manning finished 20 of 31 for 166 yards with one interception.
When it mattered most, Mr. Reliable pulled another one out.
Indy has won seven straight in this series, 12 straight over division teams and completed another sweep of its three home division games.
"It really just comes down to execution," Manning said. "They executed better than us in the first half, and in the second half, I thought our offense did a better job."
Most expected this one to be a rout.
As usual, it worked.
By grinding out 214 yards rushing, Manning and Co. spent much of the game on the sideline. It also prevented Young from making any disastrous rookie mistakes.
Young threw only two passes in the first quarter when the Titans piled up 100 yards rushing, and Travis Henry, who was inactive last week against Dallas, carried 19 times for 123 yards, his first 100-yard game with Tennessee.
The Titans finished with 214 yards rushing, and Young even gave fans a glimpse of his mobility on a nifty 19-yard touchdown run in the first quarter.
It was nearly perfect.
"It came down to us executing a play in the fourth quarter," coach Jeff Fisher said. "They did everything we asked during the week and nearly everything we asked today."
Even without defensive tackle Albert Haynesworth, who was serving the first game of his five-game suspension, running back Chris Brown, who was inactive and a makeshift offensive line, the Titans looked like they would pull off one of the most shocking upsets in the NFL for three and a half quarters.
Young marched Tennessee 88 yards on its opening possession and finished the drive by eluding several Colts tacklers to make it 7-0.
He took advantage of good field position midway through the second quarter, too, using Keith Bulluck 's fumble recovery near midfield to set up Rob Bironas ' 22-yard field goal.
Meanwhile, the Colts' offense was stuck in neutral with only seven first-downs and Manning out of sync. He couldn't even complete a pass to his favorite target, Marvin Harrison.
"We knew by watching film that we had a lot of creases we could run through," Henry said. "We did that. We still left a lot of plays out on the field."
But Manning produced in the second half, as did Harrison.
After forcing a Tennessee punt, Manning methodically moved the Colts and hooked up with Harrison on a 13-yard TD pass to make it 10-7.
Tennessee answered with a 47-yard field goal from Bironas to make it 13-7 late in the third quarter.
Manning still had too much time to work his magic and eventually rescued the Colts with a 2-yard TD pass to Wayne just inside the end zone with 5:10 left.
He finished 10 of 21 for 63 yards with one interception, but Manning got the win.
"To be 5-0 and not playing your best football is a good thing as long as you improve," Manning said. "If you stay the same way and don't improve, it's going to eventually bite you."
Harrison and Wayne each caught their first TDs of the season. ... Harrison caught a pass in his 159th straight game, breaking Marshall Faulk's NFL record for most consecutive games with a reception at the start of a career (158). ... Henry had his first 100-yard game since Dec. 7, 2003 while with Buffalo. ... Brandon Stokley left the game in the second half with a sprained left knee.