Johnson's resignation, announced Tuesday, came at the end of a 3-24 season.
The Gents, in their second year as a member of the Mid-Continent Conference, were just 1-15 in league play and did not qualify for the conference tournament.
Johnson, hired in 1999, compiled a record of 65-100.
"In April of 1999, Centenary College made a bold statement hiring me as the head men's basketball coach and the first African-American head coach in the history of the college," Johnson said. "At this time however, I feel like I have come to the end of a journey and it is time to look for some new challenges."
Before he was promoted to head coach, Johnson spent two years as an assistant to Billy Kennedy, who was fired.
Athletic Director Taylor Moore said he hopes to have a replacement hired by the first week of April.