Manning was picked three times on his first eight attempts. The last time he threw three interceptions in the first quarter was for Indianapolis on Nov. 11, 2007 at San Diego.
It was an uncharacteristic prime time start for the four-time NFL MVP, who began the night with an 11-3 career record on Mondays.
A week after Manning won his Denver debut with a home victory over Pittsburgh, the Broncos had turnovers on four of their first five possessions.
Moore ran down the left sideline 33 yards before Orlando Franklin tackled him at the 1.
Falcons running back Michael Turner ran twice over the left side of the line before jumping over a stack of Atlanta and Denver linemen to cross the ball over the goal line for a 7-0 lead with 13:20 left in the first quarter.
The Broncos ran two plays before Manning faked a play-action handoff and threw down the right seam to Eric Decker, but free safety Thomas DeCoud picked him off for a 15-yard return.
After Julio Jones dropped what would have been a 19-yard touchdown pass from Matt Ryan in the left corner of the end zone, Matt Bryant followed with a 37-yard field goal to make it 10-0 at the 9:46 mark.
Manning’s third pick went to Robert McClain, a reserve cornerback who was taking his first snap because Asante Samuel suffered a neck injury.
Atlanta nickel cornerback Christopher Owens left the game just a few seconds later with a head injury and was expected to return.
Samuel returned to the field on Denver’s next possession, whiffing on Willis McGahee’s 31-yard run but stopping Tamme 1 yard short of a first down to force a punt two snaps later.
On the next-to-last snap of the first quarter, Knoshown Moreno lost a fumble near the Denver sideline that Sean Weatherspoon recovered for Atlanta.
A scrum began after the Falcons were awarded the ball.
Broncos coach John Fox was on the field trying to restore order as players from both teams shoved each other.
As Samuel was walking away, Broncos guard Zane Beadles ran into him and knocked down Samuel.
Samuel quickly jumped up, and Atlanta defensive end Ray Edwards appeared to throw a punch at a Denver player.
Manning had a 31.2 passer rating in the first quarter.
On Sunday, Manning’s brother, Eli, threw three interceptions in the first half then rallied the New York Giants to a 41-34 victory over the Tampa Bay Buccaneers.