Orton put on an impressive passing display, going 35-of-50 through the air for 341 yards and two touchdowns with only one interception for the Broncos (2-2).
Eight of the passes went to Eddie Royal, who compiled 113 yards and a score for Denver.
Brandon Lloyd, meanwhile, had a career-best 11 receptions for 115 yards.
Tennessee (2-2) was led by Vince Young, who tossed for 173 yards and a touchdown.
Titans running back Chris Johnson was held in check by Denver, managing only 53 yards on 19 carries.