Manning's first of two TD tosses to Eric Decker midway through the second quarter ignited a stretch of 27 straight Denver points that put the contest away.
Manning completed 22-of-30 passes without an interception as the AFC West-leading Broncos (4-3) improved to 3-1 at home.
Decker finished with four grabs for 43 yards. Demaryius Thomas led the Broncos receiving corps with seven catches for 137 yards and a touchdown.
Drew Brees was held to 213 passing yards on 22-of-42 efficiency with two TDs and an interception for the Saints (2-5).
Jimmy Graham and Darren Sproles each caught a scoring pass for New Orleans.