Colter’s first role was in the film Million Dollar Baby as boxer Big Willie Little. He also guest starred on Law & Order: Trial By Jury, Law and Order: Criminal Intent, The Good Wife, ER, and The Parkers as well as several TV movies. He starred in the series Ringer.

In 2012, he was featured in the final act of the film Men in Black 3, playing agent J’s father in the year 1969.

In 2014, Colter began portraying the role of Agent Jameson Locke in the Halo franchise.  Colter starred in the series Halo: Nightfall and provided the motion capture for Agent Locke in Halo 5: Guardians, and the voice acting is performed by Ike Amadi. He also co-starred as Luke Cage in Jessica Jones on Netflix. The first season was released online on November 20, 2015.  This was followed by the character’s own series, Luke Cage, and the first season was released on September 30, 2016. The second season release followed on June 22, 2018. In between the two seasons, Colter also played Luke in The Defenders. He also starred in the 2018 alien invasion movie Extinction.

Colter was announced as the male lead in the CBS drama pilot, Evil as David Acosta, a Catholic seminarian who assesses unexplained phenomena for supernatural or scientific explanations.

In 2020, Colter starred in the Netflix anthology series Social Distance.

In 2023, Colter and Gerard Butler starred in the movie Plane by Lionsgate Play.