Taken in the fourth round (133rd overall) of the 1999 NFL Draft out of Arizona, Edwin Mulitalo gave Baltimore a raw, massive prospect who stepped directly into the fire as a rookie. He quickly claimed the starting left guard spot alongside Hall of Fame tackle Jonathan Ogden, forming a wall on the left side of the offensive line that powered Baltimore through its most iconic run in franchise history.

Mulitalo brought rare mass and raw power to Baltimore's offensive line. Positioned next to Jonathan Ogden, his main role in Brian Billick's power scheme was to reset the line of scrimmage by engaging 3-techniques and nose tackles. His hallmark was a fierce initial punch combined with powerful leg drive; once he clasped his hands around a defensive tackle's chest, he often pushed defenders aside, creating large "B-gap" openings for Jamal Lewis and Priest Holmes.

Mulitalo's physical presence was central to the identity of the 2000 Super Bowl XXXV championship team. He played all four playoff games at left guard, anchoring a rushing attack that averaged 148 rushing yards per game in the postseason and culminating in a dominant 34–7 victory over the New York Giants.

His peak performance as a run blocker came in 2003, when he started all 16 games for an offense that averaged 4.8 yards per carry and generated +62.4 Adjusted Rushing Runs (per Football Outsiders metrics). Mulitalo cleared the way for Jamal Lewis's historic 2,066-yard rushing season, including Lewis's then-NFL-record 295-yard performance against Cleveland on September 14, 2003, in which most of the internal power plays were directed right behind Mulitalo and Ogden.

After departing Baltimore following the 2006 season, Mulitalo spent two years with the Detroit Lions before transitioning into coaching and humanitarian work.  With the Ravens, he started 102 of his 106 games.