Terrell Suggs suffered a season-ending injury as the Baltimore Ravens were beaten 19-13 by the Denver Broncos.
The Ravens made a disastrous start in week one, with Suggs limping off after tearing an Achilles tendon, and the outside linebacker is expected to be ruled out for the remainder of the campaign.
Darian Stewart returned to haunt the Ravens as he snatched the ball from Crockett Gillmore in the end zone with 28 seconds left to seal the win, just months after leaving Baltimore to link up with head coach Gary Kubiak in Denver.
The Broncos held on for victory at Sports Authority Field, despite a disappointing display from veteran quarterback Peyton Manning, who made 24 of 40 for 175 yards and a paltry 59.9 passer rating.
Manning, who opted to extend his career into 2015, was sacked four times by Baltimore – his most since October 2013.
Cornerback Jimmy Smith supplied Baltimore's only touchdown and Broncos cornerback Aqib Talib responded with a 51-yard interception return for a touchdown that opened a 16-13 lead for Denver.
Opposing quarterback Joe Flacco had driven the Ravens to the Denver 16 in the final minute, but Broncos cornerback Brady Roby put his hand in Steve Smith Sr's face to deny a touchdown.