Cleveland added 12 new players to its roster before the season began, several of whom came from other AAFC teams that had dissolved as part of a selective merger of the Browns, the Baltimore Colts and the San Francisco 49ers into the NFL in 1949.
Many sportswriters and owners considered the Browns inferior despite their success in the AAFC, calling them the dominant team in a minor league, but Cleveland defeated Philadelphia 35–10, the first of 10 victories on the season.
Cleveland fell behind 28–20 in the fourth quarter against the Rams' potent offense, but quarterback Otto Graham engineered a comeback with a touchdown pass to Rex Bumgardner and a long drive that set up a winning field goal by Lou Groza with 28 seconds left to play.
Cleveland fullback Marion Motley led the NFL in rushing, and seven Browns were selected to play in the first-ever Pro Bowl, the league's all-star game.
[12] The players left over after those deals were entered into a special draft from which the Browns selected defensive end Len Ford from the Los Angeles Dons and linebacker Hal Herring from the Bills.
[16] Cleveland added several more players to its roster in the 1950 NFL draft, selecting halfback Ken Carpenter in the first round and tackle John Sandusky and guard Jim Martin in the second.
[18] Ken Gorgal, a lanky safety from Purdue, was another draft pick who earned a starting role in his rookie year, supplanting long-time starter Cliff Lewis.
[19] Both teams claimed him after the Browns entered the NFL, leading to a dispute that was settled by giving Walker to Detroit and awarding Cleveland an extra second-round draft pick.
[22] Quarterbacks Halfbacks Ends Tackles Centers Head coach Assistants Rookies in italics (7) 33 Active, 0 Inactive Cleveland held its training camp in Bowling Green, Ohio, as it had each year since its first season in 1946.
[26] The team played five exhibition games, against the Green Bay Packers, Baltimore Colts, Detroit Lions, Chicago Bears and Pittsburgh Steelers.
[30] The Browns widened the lead with another Groza field goal in the third period and a touchdown set up by a 63-yard punt return by Ken Carpenter at the beginning of the fourth.
[31] With Cleveland's best players out of the game, Detroit scored two touchdowns in the fourth quarter on a pair of two-yard rushes by Dan Sandifer and John Panelli.
[32] Near the end of the quarter, Jones fell as he caught a pass from Graham, but managed to get back up and run it in for a touchdown, giving the Browns a 17–10 lead at halftime.
[32] Neither team scored in the third quarter, but the Browns began to pull away at the beginning of the fourth when Carpenter took a high punt by Fred "Curly" Morrison on his own 21-yard line and returned it for a touchdown.
[34] The victory over the Bears, who finished near the top of the NFL's Western Conference in 1949, appeared to prove that the team could compete in the new league, but Eagles coach Greasy Neale did not take the Browns seriously.
[34] Led by an offense that featured Graham, Motley and Lavelli, all of whom were later inducted into the Pro Football Hall of Fame, the Browns beat the Eagles in Philadelphia and went on to finish the regular season with a 10–2 record for first place in the league's American Division.
[36] The Browns added two touchdowns toward the end of the game, the first on a one-yard quarterback sneak by Graham and the second a short run by Bumgardner that was set up by a Lahr interception.
[42] Cleveland had several opportunities to score late in the game, including a drive set up by a good punt return by Dom Moselle that ended with a fumble.
[43] Moselle returned a punt 46 yards to Pittsburgh's 19-yard line later in the period, leading to a drive that ended with a one-yard touchdown on a quarterback sneak by Graham.
[43] An errant snap on the Steelers' first play in the second half rolled into their own end zone, where Lynn Chandnois recovered but was tackled by John Kissell for a safety.
[44] Chicago scored a touchdown on their first possession, assisted by a defensive holding penalty against the Browns that gave the Cardinals a first down at Cleveland's three-yard line.
[47] After stopping a pair of long Pittsburgh drives in the second quarter, Cleveland advanced to the Steelers' two-yard line but had to settle for a Groza field goal.
[48] The Cardinals stopped a long Cleveland drive in the fourth quarter that reached their two-yard line, but they were unable to score on their ensuing possession as time expired.
[49] The Browns' Chubby Grigg recovered a fumble by San Francisco's Sam Cathcart at the 49ers' seven-yard line near end of the first quarter, setting up a short touchdown pass from Graham to Jones.
[49] A 22-yard rushing touchdown by Motley put the Browns ahead midway through the second quarter, but San Francisco tied the game at the end of the half with a pass from Albert to Alyn Beals.
[49] Groza added to the lead with another field goal in the fourth quarter, and the Browns surged ahead at the end of the game by capitalizing on San Francisco interceptions and fumbles.
[58] The Rams had been based in Cleveland before departing for Los Angeles in 1946, the year the Browns started play, and had won the NFL championship in 1945, when quarterback Bob Waterfield was a rookie.
[60] Graham and the Browns' offense responded with a drive later in the first quarter that evened the score, but the Rams went ahead again by a touchdown on a three-yard Hoerner rush.
[67] Speedie and Willis also made it on sportswriters' first-team All-Pro lists, while Graham, tackle Lou Rymkus, guard Lin Houston, fullback Tony Adamle and defensive back Tommy James were selected as second-teamers.
[67] Motley, Speedie, Willis, Graham, Adamle, Groza and guard Weldon Humble were also selected for the first-ever Pro Bowl, the NFL's all-star game.