INDIANAPOLIS -- For Brock Osweiler, it was a matter of being ready when called upon.

Osweiler was Thursday night, throwing for two touchdowns and running for another to lead the Denver Broncos to a 25-13 victory over the Indianapolis Colts.

Osweiler came into the game after starter Trevor Siemian left with what Broncos coach Vance Joseph called a left shoulder sprain after a sack in the first quarter.

"He played well," Joseph said of Osweiler. "He played with great poise. He played clean, smart football to get the win."

Osweiler completed 12 of 17 passes for 194 yards.

Broncos running back C.J. Anderson gained 158 yards on 30 carries.

Osweiler said the play of Anderson and the offensive line opened things up for the passing game.

"Any time you can run the football with that kind of success, you are going to get man-to-man coverage outside," Osweiler said. "DT (Demaryius Thomas), Emmanuel (Sanders) and Cody (Latimer) can all take advantage of one-on-one coverage."

It was the fifth straight loss for the Colts (3-11). The Broncos (5-9) won their second in a row after snapping an eight-game slide.

Osweiler credited offensive coordinator Bill Musgrave for calling the plays.

"There were no nerves but it takes about a series to warm up," Osweiler said. "The quarterbacks have all studied hard. You don't know who is going to be playing week to week."

After the Colts increased their lead to 13-7 on a 39-yard field goal by Adam Vinatieri in the third quarter, the Broncos scored the final 18 points.

Joseph said the team responded very well to adversity.

"We were down 10-0 and we outscored them 25-3 after that," Joseph said. "No one blinked. We were playing well in all three phases. So why panic, just keep playing."

The Broncos took the lead on a 22-yard touchdown pass from Osweiler to Latimer to take a 14-13 lead with 4:16 left in the third quarter.

After a three-and-out by the Colts, Osweiler completed a 54-yard touchdown pass to Jeff Heuerman and then a two-point conversion pass to Latimer to push the lead to 22-13 with 2:37 to go in the third quarter.

Denver boosted the lead to 25-13 on a 40-yard field goal by Brandon McManus with 5:13 remaining.

"Another disappointing loss," Colts coach Chuck Pagano said. "I was pleased with how we started the game. It's what we talked about all week, with a short week. Just again didn't have enough to finish in the second half."

Colts quarterback Jacoby Brissett completed 17 of 30 passes for 158 yards.

"We just have to find a way to get over the hump," Brissett said. "I got to do a better job of doing my job. I got to make plays in those critical situations."

Indianapolis running back Frank Gore was limited to 31 yards on 10 carries.

In the third quarter, the Colts lost linebackers Jeremiah George (neck) and Jon Bostic (knee), and right guard Denzelle Good left with a knee injury.

Sanders had seven catches for 68 yards for Denver but left the game in the third quarter with a right ankle injury.

The Colts led 10-7 lead at halftime.

Kenny Moore II made his first career interception on the Broncos' first possession, picking off Siemian and returning it 25 yards to the 50. The Colts scored on a third-and-2 from the 7 as Brissett scrambled up the middle for a 7-yard touchdown run to put the Colts up 7-0.

The Broncos drove to the Colts 7 before things broke down. After two incomplete passes, Siemian was injured on a sack by linebacker Barkevious Mingo and was forced to leave the game. Following a delay-of-game penalty, McManus missed a 40-yard field-goal attempt with 1:30 left in the opening quarter.

Osweiler replaced Siemian on the next possession.

The Colts drove 59 yards in 10 plays before settling for Vinatieri's 45-yard field goal in the second quarter.

On the ensuing possession, the Broncos went 75 yards on 11 plays. Osweiler, who had completions of 22 and 17 yards on the drive, scored on an 18-yard scramble up the middle.

NOTES: Colts TE Brandon Williams was hurt on a Colts' punt in the first minute of the second quarter and was carted off the field in a stretcher with a head injury. Williams had movement and there was no neck injury. He was strapped in as a precaution. He was later treated and released with a concussion. ... Colts C Ryan Kelly missed his third consecutive game with a concussion. Kelly was replaced by Mike Person. ... WR Chester Rogers started in place of Donte Moncrief, who was out for the second game in a row with an ankle injury. ... The Broncos put SS Justin Simmons on injured reserve. Simmons was injured while celebrating Brandon Marshall's strip-sack of Jets QB Josh McCown in Sunday's 23-0 shutout by Denver. Will Parks started in Simmons' place.