Mayfield led the way for Cleveland with 188 passing yards and two touchdowns, and Nick Chubb added 100 yards on the ground.
Meanwhile, Case Keenum threw for 257 yards, zero touchdowns and two interceptions in a losing effort.
It marks the Browns' fourth win in their last five games.
Baker Mayfield's Toughness to Fight Through Mistakes Makes Browns Dangerous
Many of Cleveland's recent victories have come because of Mayfield's strong play.
Week 15 served as a reminder to the 23-year-old passer that life in the NFL isn't always so easy. But those struggles should be viewed as normal growing pains, not reason to panic.
Mayfield's night, oddly enough, got off to a strong start, as he completed two of his first three pass attempts while leading the Browns to an opening-drive touchdown:
That made Mayfield the first Browns quarterback since Derek Anderson in 2007 to throw 20-plus touchdowns in a single season. The rest of the night would not be so easy, though.
Mayfield would go on to complete just five of his final 15 passes during the first half for 56 yards. That included a brutal interception with Cleveland in field-goal range with a chance to take the lead into halftime.
And after completing six of his first seven passes of the third quarter, another Mayfield mistake—this time a fumble—thwarted a second chance for Cleveland to take the lead.
Even after struggling for the first three quarters, Mayfield found a way to get the job done in the fourth. He proved he had a short memory while leading the Browns to the go-ahead score:
Not only that, but he helped the Browns milk nearly three minutes off the clock while clinging to a one-point lead.
It would be easy for critics to jump all over the rookie following an ugly performance. However, it wasn't the easiest of circumstances to play in, with it being a national television game against a playoff contender at high altitude.
Still, he found a way to win the game.
That's not even mentioning the fact that the Broncos have one of the top pass rushes in the NFL. Denver entered Week 15 tied for fourth with 40 sacks, led by former Super Bowl MVP Von Miller (13.5 sacks, plus one against the Browns) and Defensive Rookie of the Year candidate Bradley Chubb (12). That's a tough duo for any quarterback to face, let alone someone making just his 11th career start.
Don't forget, Mayfield entered the game having completed 64.4 percent of his passes, including 74.8 percent over the last four games. While he does need to take better care of the football (seven fumbles on the season, four interceptions in the last three games), his inaccuracy against the Broncos appears to be a blip on the radar rather than a worrisome trend.
Mayfield is still prone to growing pains, but with him under center, this Browns squad has been competitive.
Broncos' Rookie Class Provides Hope for Future
While Cleveland's rookie class of Mayfield, Nick Chubb and Denzel Ward has been the talk of the league this season, Denver's youngsters should not be ignored.
Bradley Chubb and his 12 sacks get all of the attention in Denver, especially as he chases the rookie sack record (14.5). But he is far from the only rookie contributing for the Broncos.
Running back Phillip Lindsay (991 yards) is closing in on a 1,000-yard season while averaging an impressive 5.4 yards per carry. Although he had a quiet night on Saturday (24 yards) and in Week 14 (30 yards), he piled up 267 yards in the prior two games.
Second-round pick Courtland Sutton has started to emerge since the October trade of Demaryius Thomas. He had 248 yards and one touchdown in the five games since the trade. Add in five catches for 42 yards against the Browns, and he looks like an impact player in the passing attack.
Meanwhile, fourth-round pick DaeSean Hamilton is starting to show what he can do. After being held to just five catches for 61 yards through the first 13 weeks, he hauled in seven receptions for 47 yards against the San Francisco 49ers last week. He nearly replicated that performance against the Browns, putting up 46 yards on seven catches.
Ultimately, though, Denver couldn't make enough plays in Week 15 to escape with a victory.
The Broncos are almost completely eliminated from playoff contention after losing to the 49ers and the Browns the last two weeks. And while that outcome is a bummer after the team got off to a 2-0 start this season, this year's rookie class gives Denver fans hope that the franchise will return to the postseason at some point in the near future.
Cleveland (6-7-1) will return home to host the Cincinnati Bengals on Sunday, Dec. 23. Denver (6-8) will play its final road game of the season in an AFC West battle against the Oakland Raiders on Monday, Dec. 24.