After pursuing a baseball career from 2002 to 2006, Weeden played college football for the Oklahoma State Cowboys, where he was a first-team All-Big 12.

Weeden served as the Browns' starter during his rookie season and spent the remainder of his career as backup on the Dallas Cowboys, Houston Texans, and Tennessee Titans.

[1] After the 2003 season, he was traded to the Los Angeles Dodgers with Jeff Weaver and Yhency Brazobán for Kevin Brown.

[3] Weeden played his last season of professional baseball in 2006 for the Class-A High Desert Mavericks of the California League.

In Week 2, Weeden suffered a severe injury to his thumb, which led to two interceptions and two fumbles in a win over Troy.

He also broke school records in total attempts, completions, yardage, and touchdowns (all which were previously held by incumbent Coach Mike Gundy).

[14] In his first game, Weeden had a 5.1 passer rating after throwing four interceptions in a loss to the Philadelphia Eagles, which is the sixth lowest in a season opener by any quarterback attempting at least 15 passes since the merger in 1970.

[15] However, one week later, he was much improved throwing for 2 touchdowns, completed 26 passes on 37 attempts for 322 yards, no interceptions with a passer rating of 114.9.

During Week 6, Weeden celebrated his 29th birthday by completing 17 passes on 29 attempts for 231 yards and 2 touchdowns en route to his first NFL win by defeating the intrastate rival Cincinnati Bengals.

[16] In the Browns victory over the Pittsburgh Steelers in Week 12, Weeden's helmet collided with Joe Thomas' knee, giving him a concussion.

Weeden won the starting job for the 2013 season, but injured his thumb in the fourth quarter of Week 2 in a 14–6 loss at Baltimore.

He smashed his thumb on the helmet of left guard John Greco while throwing a pass and had to leave the game for treatment and X-rays.

The Browns won their first game of the season the next week under 3rd string quarterback Brian Hoyer, with Weeden sidelined by his thumb injury.

On September 28, Weeden admitted that he was not guaranteed to reclaim the starting quarterback position over Hoyer when he returned from injury.

On October 23, Weeden was once again benched, this time in favor of Campbell, for the Browns' Week 8 matchup vs. the 7–0 Kansas City Chiefs.

Following a Week 8 back injury to Tony Romo, Weeden was named the starter in a 28–17 loss against the playoff bound Arizona Cardinals.

It was announced that Romo would be placed on short term IR, which left him designated to return November 22, and that Weeden would be the starter at quarterback.

Even though he was preparing to be the starter, with owner Jerry Jones and head coach Jason Garrett commenting on his positive progress the Cowboys covered themselves by trading for Matt Cassel on September 22.

On November 17, Weeden was waived to make room for Romo, with the team deciding to keep Cassel as the main backup.