Despite the fact that Darden had little trial experience, Darden was selected to assist Clark in Simpson's prosecution. The fact that Darden was an African-American was significant because the Simpson jury was comprised mostly of African-Americans, Cochran had joined the defense team, and the victims were white. In bringing Darden on, the prosecution hoped to dispel the view that this matter was a racist "white against black" prosecution.

Seemingly overwhelmed by the defense team, and often fumbling objections and the introduction of evidence, Darden may have been intimidated by Cochran, a significant figure in the African-American community. Despite the fact that Darden's abilities during the trial increased, he received criticism during the trial from legal observers. His worst blunder may have been his request that Simpson try on the "bloody gloves," which seemed not to fit.

Darden's argument to the court regarding the admissibility of Fuhrman's use of the word "nigger" brought great reviews for the passionate delivery. "It is a dirty, filthy word. It is not a word that I allow people to use in my household." Darden said that the use of the word would upset black jurors and make them have to decide which "side" they were on, "the side of the white prosecutors and white policeman, or on the side of the black defendant and his very prominent black lawyer."

Darden delivered half of the prosecutions closing statement, arguing that with each domestic abuse incident, "the fuse was burning" and finally resulted in Simpson murdering his ex-wife, Brown-Simpson, and Goldman as a result.

After the Simpson trial, Darden took a leave of absence from the District attorney's office. He is not expected to return. Darden wrote a successful book about the trial and accepted a position as a professor at the Southwestern University School of Law in Los Angeles.