After a Green Bay field goal to start the game, the Colts marched down the the field on their first possession. Dominic Rhodes scored on a three-yard run, and the Colts led, 7-3.
It would be the last time the Colts would score for 61 offensive plays, as Green Bay built a 17-7 halftime lead, behind a 16-of-19 passing performance from Aaron Rodgers and 71 yards from Ryan Grant in the first half.
Ryan Grant leaves Antoine Bethea behind on a touchdown run
The Packers' defense did the rest, as Nick Collins took back a Manning pass 62 yards for a score and a 24-7 lead. Mason Crosby added a field goal in the third quarter, and the Packers led, 27-7, heading into the fourth quarter.
The Colts have overcome more difficult circumstances in the past — most notably in their rally to win in Houston two weeks ago — but the Packers had the Colts on the ropes and weren't letting them back up.
When Manning led the Colts within sight of the end zone with about five minutes left in the game, Green Bay defensive back Aaron Rouse jumped on a Manning pass intended for Anthony Gonzalez and returned it 99 yards for a touchdown and a 34-7 lead.
The Colts would add a meaningless touchdown late, but even that didn't come easy, as Indianapolis had two touchdowns overturned by official review before Rhodes scored from one yard out for the final margin.
A week after achieving a gaudy 134.7 quarterback rating and being named the AFC Offensive Player of the Week, Manning completed just 21-of-42 pass attempts for 226 yards and a 46.6 rating.
Much of the credit goes to the Green Bay secondary, which shut down the Colts star wide receiver tandem. Reggie Wayne had just two catches for 24 yards and Marvin Harrison had two receptions for 11 yards.
And a week after the Colts racked up four sacks against the Baltimore Ravens, the Colts managed zero sacks and were only credited with three quarterback hurries.
The Colts were also flagged for 12 penalties for 110 yards, the highest total ever for a Tony Dungy-coached team. The 3-3 Colts travel to Nashville next week to take on the league's last undefeated team, the Tennessee Titans, on "Monday Night Football."