Omoni began her movie career with her first movie role in Bitter Encounter (1996), where she played a secretary. Her next was Shame. She then went on to play the lead female character in three major movies; Not My Will, Destined To Die and Another Campus Tale. After enjoying a brief career in 1996, Omoni left the movie industry to complete her university education. She married immediately after school and did not return to the industry until a decade later.

Omoni has several screenplays to her credit, including her film Wives On Strike as well as The Rivals, a movie she co-produced with her friend and won the prize for Best International Drama at the New York International Independent Film & Video Festival. It was the first Nigerian film to be premiered since the festival’s inception in 2003. The movie was given a 3-star rating out of 4 by the festival’s judges.

In 2010, she won the award for Best Actress Narrative Feature at the Los Angeles Movie Awards, and the award for Best Actress at the Harlem International Film Festival. Omoni was nominated for the Best Actress in a leading role award at the 2011 Africa Movie Academy Awards.

In 2014, she won Big Screen Actress of the Year award, at the 2014 ELOY Awards, for her movie Being Mrs Elliott. In 2015, Omoni was awarded the Sun Nollywood “Personality of the Year”, She has directed several movies such as Being Mrs Elliott, The First Lady, Wives on Strike, and Okafor’s Law.

On 14 August 2017, Omoni Oboli took to her instagram page to share a post announcing her new deal as the Brand ambassador of Olawale Ayilara’s LandWey Investment Limited.

Omoni Oboli starred in the movie Okafor’s Law, which premiered on 24 March 2017. However, the movie could not be screened at the premiere due to an injunction by the court. Oboli was accused of copyright infringement by Jude Idada, who claimed to have written part of the script for Okafor’s Law. The movie was released on 31 March 2017.