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 tackle after playing at 295 pounds during his senior year at Virginia, Ferguson officially weighed in at 312 for the NFL combine. As a 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 a tackle was 1988, when they selected Dave Cadigan of USC at No. 8.
Ferguson's hometown of Freeport, New York, dedicated a street to him on September 29, 2009. South Ocean Avenue, where he grew up, received secondary signage as D'Brickashaw Ferguson Way. His father Ed Ferguson Sr is a native of Nassau, Bahamas and his older brother Edwin also graduated from UVa. Ferguson married Kirsten Speller on July 2, 2011. He is also a black belt in Karate.
Ferguson was the inspiration for Key & Peele's East-West College Bowl sketch, where Key and Peele imitate football players with humorous names and introduce themselves. In the most recent version of said Bowl, real players including D'Brickashaw were used.