Josh McCown was not cleared from the NFL's concussion protocol and is not able to practice Friday.
Manziel has taken all first-team reps this week leading up to the third start of his career. In his first two starts, both losses, he completed 13 of 26 passes with zero touchdowns, two interceptions and a total quarterback rating of 2.6.
"I definitely feel I'm in a lot better place now," Manziel said Friday. "So I guess if I thought I was prepared then, I think I'm even more prepared now, obviously with the experience and those two starts and then through the offseason and last week and just where I'm at today, so I definitely feel a lot better."
It will be a Heisman vs. Heisman matchup at quarterback, as Manziel squares off against Marcus Mariota.
According to the Elias Sports Bureau, Mariota will be the first Heisman-winning quarterback to face quarterbacks who have also won the award in consecutive weeks at any point in a single season. He won his debut against Jameis Winston last week.
"Their defense presents a lot of problems, and I think we'll have more than enough to worry about then to think of looking up and trying to compare stats," Browns coach Mike Pettine said. "The only thing he's going to worry about is the scoreboard."
McCown left the season opener against the New York Jets after taking a hit to the head late in the first quarter. Manziel threw a touchdown pass in relief of McCown in the first half but finished with three second-half turnovers.
"We knew he was going to be the guy, and coming out of playing three quarters against the Jets, looking back on it now, that experience helps him," Pettine said.
Manziel had missed the final two preseason games and a little more than two weeks of practice with tendinitis in his right elbow.
Offensive coordinator John DeFilippo, though, said he saw a clear difference between Manziel's performance last season and the way he played in the opener.
"Johnny losing these last three weeks of practice, he didn't drop off from a level of accuracy, footwork and those things that a lot of young quarterbacks do," DeFilippo said. "Johnny has tremendous physical attributes, tremendous physical attributes. We just have to keep grooming him and keep teaching him situational football and when to take chances and when not to."
Asked whether he viewed this game as an opportunity to seize the starting job, Manziel said he isn't looking past this week.
"It's really go into this game, do my best, and from there on, we'll see what happens," he said.
ESPN Stats & Information contributed to this report.