The record-setting touchdown toss gave the Saints a 26-6 lead with 2:36 remaining in the second quarter of the contest and gave Brees a career total of 71,968 yards, eclipsing Manning's former mark of 71,940 after having supassed what had been the second-best career total of 71,838 yards by Brett Favre on a 75-yard touchdown drive earlier in the quarter.
The running back played 13 snaps in the blowout loss, just three of which came after halftime - he didn't touch the ball on any of those plays - per Next Gen Stats.
Brees' family was gathered on the sidelines so he could share the moment with them.
Drew Brees became the NFL's all-time leader in yards passing - and he did it with a certain panache and precision that made the 39-year-old quarterback look far from finished.
Brees had 12,238 passing yards as a member of the then-San Diego Chargers from 2001-05, but his assault on the National Football League record books truly began when he joined the Saints as a free agent in 2006.
"Also, let this serve as the congratulations for the touchdown record because as you can see, I'm very busy", Manning added.
"All your hard work and dedication has paid off", Manning said in a pre-taped message.
Drew Brees set an National Football League record on Monday night, and he did so in awesome fashion.
"I didn't set out on this journey to break these records". Brees has passed for more than 59,000 yards and more than 400 TDs in 12-plus seasons for New Orleans, smashing every meaningful Saints passing record while helping long-frustrated franchise win its first Super Bowl in 2010 and go to the playoffs six times. Brees completed passes to nine different receivers, including one he completed one to himself on a tipped pass at the line of scrimmage.