Before the 2003 NFL Draft, Vince Manuwai made headlines at the combine by bench-pressing 225 pounds 35 times, signaling the sheer functional strength he brought from Hawaii to North Florida. Placed into the starting lineup at left guard as a third-round pick (72nd overall), he adapted instantly to the speed of the professional game, starting 12 contests as a rookie and claiming a spot on the PFWA All-Rookie Team.

Manuwai quickly emerged as the bone-crushing engine behind Jacksonville's premier rushing attack. Playing alongside center Brad Meester, his aggressive, physical blocking at the point of attack regularly cleared wide lanes for Fred Taylor and Maurice Jones-Drew during the team's most potent mid-2000s offensive campaigns. Manuwai produced his finest football during the 2006 and 2007 seasons, serving as the lead interior blocker for back-to-back top-three NFL rushing offenses—including a franchise-record 2,541 rushing yards in 2006. Though a torn ACL interrupted his momentum in 2008, he battled back to reclaim his starting job and anchor the line for two more seasons before concluding his eight-year playing career spent entirely in Jacksonville.

He would make 105 starts in 111 games over his career.