The Denver Broncos quarterback became the sixth player to throw for that many and the first since Joe Kapp on Sept. 28, 1969.
The others read like a who's who of passers who defied the 3-yards-and-a-cloud-of-dust days long before the NFL became so pass-happy: Sid Luckman, Adrian Burk, George Blanda and Y.A. Tittle.
"It was an awesome night," Manning told NBC after the 49-27 Broncos victory. "Our offensive line did a heck of a job against a great pass rush, gave me good time."
"Baltimore's got a great defense; we had to be patient," Manning told NBC. "We knew we could get some shots. We were great down in the red zone. That and inside the 30-35, we took some shots, got some space there and our receivers made some big plays."
Manning was 27-of-42 for 462 yards with no interceptions for an off-the-charts quarterback rating of 141.1.
"Peyton had an amazing night," Broncos coach John Fox said. "Peyton's had a lot of amazing nights."
Wearing an orange-and-gray glove like the one he wore on that icy January night the previous time these teams met -- a Baltimore win in the playoffs -- Manning took a while to get warmed up against a Baltimore defense that had to replace seven Super Bowl starters.
He ditched the glove once the rains stopped -- and then he was unstoppable.
"I felt like we had to keep scoring because Baltimore can score at any time," Manning said.
Manning's seventh TD pass covered only a few yards in the air but Demaryius Thomas, a former first-round pick, hauled in the pass in the left flat and turned on the jets, racing past several gassed defenders for a 78-yard play that capped Denver's big night.
"Didn't surprise me a bit," said the Ravens' Brandon Stokley, who played with Manning in Denver and Indianapolis. "He's capable of this kind of night."
"He's phenomenal. To continue to come out every year and put that kind of performance on for us, it's amazing," Julius Thomas said.
Information from The Associated Press was used in this report.