Moulds was the Bills' first round draft pick (24th overall) in 1996. For his first two seasons, Moulds was stuck on the depth chart behind receivers Andre Reed and Quinn Early.
Moulds finally had his breakout season in 1998, where set a single-season team record with 1,368 receiving yards, a total that led the AFC and was second in the league. (Moulds also has the Bills' second-highest single-season total, with 1,326 in 2002.) Moulds's 20.4 yards per catch was second in the NFL in 1998.
In his eight seasons as the number one receiver for the Bills (1998-2005), Moulds had 626 receptions for 8,523 yards, an average of 78.25 catches and 1,065 yards per season. Moulds's yardage was 7th-most in the NFL over that span.
In 2002, Moulds became the first player in Bills history to log 100 receptions in a single season.
In the playoffs Moulds had NFL playoff record 240 receiving yards against the Miami Dolphins, though he notably lost a fumble on the Bills' first play, a 65-yard pass from Flutie. Buffalo lost 24-17.
Moulds established himself as one of the premier receivers in football in the late 1990s and early 2000s, amassing 675 career receptions (as of the end of 2005) and being selected to three Pro Bowls (1998, 2000, 2002).
On April 4, 2006, Moulds was traded to the Houston Texans, in exchange for their fifth round draft pick in the 2006 NFL Draft. Moulds was released from the Texans after the 2006 season. After his release, Moulds criticized then-Texans quarterbackDavid Carr, saying "[t]he quarterback has to show that he can carry [the team]."
The Tennessee Titans signed Moulds on July 25, 2007, and at the beginning of the season he had earned a starting position. Moulds played in all 16 games in 2007, having the 4th most receptions on his team, 2nd most by wide receivers, with 32 catches for 342 yards. The Titans released Eric Moulds after the 2007 season.