McCarron started the game and completed 3 of 6 passes for 12 yards. He was sacked once in the first quarter but remained in the game until early in the second.
In four offensive possessions Friday with McCarron at quarterback, the Bills' first-team offense gained 7 yards and did not earn a first down.
"All I really know right now is that he hurt his right shoulder," Bills coach Sean McDermott said. "He'll have some more tests when we get back."
McCarron was replaced by rookie first-round pick Josh Allen, who led the Bills' first-team offense on an 80-yard touchdown drive in the second quarter. Allen played three possessions, completing 9 of 13 passes for 60 yards and a 2-yard touchdown pass to wide receiver Rod Streater. He was replaced by Nathan Peterman in the third quarter of Buffalo's 19-17 win.
Buffalo now is tied with the Tampa Bay Buccaneers for the worst Super Bowl odds (200-1) at the Westgate Las Vegas SuperBook.
The Bills have rotated their quarterbacks throughout training camp and the preseason as part of a three-way competition for the starting job. Peterman started the preseason opener before being replaced in that game by McCarron, who went 7-of-10 passing for 116 yards. Peterman and McCarron have generally split first-team snaps in practice.
McCarron signed a two-year, $10 million contract with Buffalo in March after four seasons with the Cincinnati Bengals. The deal included a $4 million signing bonus, a fully guaranteed $900,000 base salary in 2018 and $1.1 million of his 2019 base salary guaranteed for injury.
Meanwhile, Allen looked good in a performance the Bills might need more of sooner than expected.
"Tonight we wanted to see him in the second quarter and look at him with increased talent level on the other side of the ball and on our side of the ball," McDermott said. "I thought he did some good things."
On his first drive of the game with the Bills trailing 7-0 and the offense having done nothing against the Browns' first-string defense, Allen completed 4 of 6 passes for 29 yards and a touchdown. Following a rocky start in which he left Kelvin Benjamin out to dry on a play over the middle, the rookie settled in and hit four of his next five passes.
On third-and-goal from the 2, Allen looked more like the rookie on the other sideline, Baker Mayfield, as he eluded pressure and created a passing lane for a touchdown toss to Streater for the Bills' first points of the night.
"That's certainly one of his strengths in terms of the skill set that he brings to the table. We saw that in college," McDermott said. "But at the end of the day, you have to win from the pocket, and I thought he made some good throws from the pocket tonight."
The next drive for Allen started on the Browns' 41 with 1:40 left in the first half after a 39-yard punt return by Marcus Murphy. Allen ran the 2-minute offense effectively, leading to a field goal and a 10-7 halftime lead. On the drive, Allen showcased his feet as much as his huge arm.
"It's a continuing struggle for quarterbacks when you feel pressure breaking down in the pocket and not trying to get out too fast and knowing when the right time is," Allen said. "That just kind of comes with game reps."
While McDermott continued to say the staff would have to "look at the tape" before making any evaluations at the quarterback position, especially if McCarron's injury is indeed a fracture, he said the Bills like what they see in Allen.
"So far overall I would say he has been pretty steady, mentally, and that's a great quality," McDermott said. "I think the guys appreciate that. For a rookie to have that quality is important. The mental toughness element, if you will, that is so important to manage the highs and lows of life in the NFL."
Information from ESPN contributor Ryan Isley was used in this report.