Speight was born in Baltimore, Maryland, the son of Gussie Watson and Walter Speight. He graduated from Old Mill High School in Millersville in 1981, where he is in the Hall of Fame for starring in three sports: football, track, and basketball. He attended Morgan State University from 1981 to 1985, and was a Division 1 All American Linebacker. After graduating in 1985, he tried unsuccessfully to play in the NFL. Not one to give up easily, he tried out for the United States Football League the same year. During tryouts, he ran the 40-yard dash in 4.3 seconds, which got the attention of the Baltimore Stars. Speight and Business manager/cousin Butch Groover negotiated a two-year deal with the Stars for more than $200,000. However, the USFL folded before he even played one season. He never made it into the NFL.

Speight moved on to professional wrestling working for Global Wrestling Federation and Catch Wrestling Association as "Rasta the Voodoo Man". It was not long, however, before he quit wrestling in 1997, to pursue an acting career.

In 2003, Speight appeared in a Reebok commercial that aired during the Super Bowl. The role was based on a character that Speight had played in a short independent film in 2000. In the commercial, Speight plays Terry Tate, an office linebacker charged with the enforcement of office policies. For Example, when one employee finishes the office's coffee and fails to begin brewing more, he is quickly tackled by Tate, who stands over the man, screaming "You kill the joe, you make some mo'!" Within the commercials, Speight promotes recycling, dutiful work, and several other courteous actions. The commercials received critical acclaim, and according to The Hollywood Reporter was the most watched part of the Super Bowl by TiVo viewers. The Office Linebacker spots returned in 2008 and later 2016 as part of a campaign in support of voting. In 2008 they featured several notable shorts of Terry Tate tackling a blind-sided Sarah Palin who had previously struggled in responding to questions posed by journalists including interviews by Katie Couric leading up to the 2008 Presidential election. Tate emphasized the importance of reading and providing lucid responses during media interviews. Returning again in 2016 under the moniker, "TERRY TATE MAKES AMERICA GREAT", the new target of the Terry Tate etiquette campaign became the then Republican presidential nominee Donald Trump after controversial video surfaced of Trump making disparaging statements about women.

Speight also had a recurring role on Damon Wayan's ABC series My Wife and Kids as Calvin Scott, the father of Vanessa Scott. For the 2006 Xbox 360 game Gears of War, Speight voiced the role of former "Thrashball" player Augustus Cole (a.k.a. Cole Train), humorously re-using some of his characteristic lines. He won the G-Phoria '07 award for Best Voiceover. Speight later reprised the role for Gears of War 2 in 2008, Gears of War 3 in 2011 and Gears of War: Judgment in 2013

Speight guest-starred as prison inmate Banks on the show Prison Break. Speight also had a role in the 2007 Eddie Murphy motion picture Norbit as Blue, one of the three brothers of Rasputia. He also appeared in Harold & Kumar Escape from Guantanamo Bay, as a character who is interrogated using racist methods. He then had a small role in the film Bachelor Party Vegas, as Gold Tooth, a prison rapist.

Speight appeared in an episode of ESPN's Mayne Street comedy short. In the 2008 TV film Ring of Death, Speight played convict "Milton Kennedy", a feared and revered gang boss (nicknamed "The President"), and undefeated champion of an underground fighting tournament in a notorious prison.

In 2009, Speight appeared in an episode of Bones, "Double Trouble in the Panhandle", where he played the Traveling Circus' strong man "Magnum".