While attending the University of Virginia, Ferguson played for the Virginia Cavaliers football team. He started his college career listed at 260 pounds (118 kg), often dropping to 245 pounds (111 kg) through the regular season. He started 49 games for the Cavaliers, and he was named to the consensus All-America first team during his final season. He was placed on the all-Atlantic Coast Conference first team two years in a row, and he became Virginia's first All-ACC offensive tackle since 1998. Ferguson started at left tackle in four consecutive bowl games for the Cavaliers. He played linebacker on a special defensive package employed sparingly in 2003. He did this while earning a religious studies degree in only 3.5 years. He was an All-America selection in 2004 by Pro Football Weekly.
Considered an undersized offensive tackle after playing at 295 pounds during his senior year at Virginia, Ferguson officially weighed in at 312 for the NFL combine. As an offensive tackle, Ferguson's talent is found in his lower body strength, athleticism and flexibility. This athleticism and flexibility is further evidenced in his attaining a black belt in Shotokan karate and brown belt in taekwondo. Adding to that ability is his natural build, as Ferguson has an armspan of 87 inches (221 cm).
Ferguson was one of six players the NFL invited to New York for the 2006 NFL Draft events. He was selected 4th overall by the New York Jets. The last time the Jets used their first pick on an offensive tackle was 1988, when they selected Dave Cadigan of USC at No. 8.
Ferguson finally reached the NFL when the New York Jets drafted him with the 4th pick overall after Vince Young was chosen by the Titans. On July 26, 2006, Ferguson signed a five-year deal with the Jets that was similar to the $35 million deal that 2005’s No. 4 pick, Cedric Benson, signed with the Chicago Bears. Designated as Jason Fabini's successor, Ferguson started every game at left tackle for the Jets since the beginning of the 2006 NFL season. On January 8, 2010 Miami Dolphins Tackle Jake Long withdrew from the 2010 Pro Bowl due to injuries and Ferguson was named as his replacement. He was invited to the 2011 Pro Bowl.
Ferguson's home town, Freeport, New York, has dedicated a street to him. On September 29, 2009, South Ocean Avenue, where he grew up, received secondary signage as D'Brickashaw Ferguson Way. D'Brickashaw Ferguson is a black belt in Karate.