Sam, the first openly gay active player in NFL history, mocked Manziel's "money sign" after sacking the Heisman Trophy winner in the fourth quarter of the St. Louis Rams' preseason victory over the Cleveland Browns.
Sam, a seventh-round draft pick who is competing for a roster spot with the Rams, recorded the first of his two sacks of Manziel with just under 11 minutes remaining, punctuating the play by celebrating with the "money" sign.
"If you're going to sack Johnny, you've got to do that once," Sam said.
Sam also sacked Manziel on the final play of the game, recording his third sack this preseason.
Just five days after struggling in Cleveland's preseason game against the Washington Redskins, Manziel fared better Saturday, completing 10-of-15 passes for 85 yards and also running for a 7-yard touchdown.
"He's a talented kid," Sam said. "He isn't called Johnny Football for nothing. It was fun getting to play against Manziel in an NFL game. I sacked him as both a junior and senior at Missouri."
Sam and Manziel also briefly met prior Saturday night's game. Manziel said he was impressed with Sam's performance during the contest.
"The guy goes through a lot of stuff, so he gets heckled by everybody I'm sure, so he came up to me and said hello," Manziel said of the pregame meeting. "It was a brief interaction. I thought he played pretty well."
The Browns named veteran Brian Hoyer as their starting quarterback over Manziel this past Tuesday, although first-year coach Mike Pettine acknowledged later in the week that the team might consider playing both quarterbacks at some point this season.
ESPN.com's Jim Trotter and The Associated Press contributed to this report.
Sam On Sacking Manziel: 'Big Play For Me'
Johnny Manziel and Michael Sam discuss their preseason matchup, including the fourth-quarter sack Sam registered on Manziel.