In 1980 Jim McCloskey decided to leave the corporate world and enter the ministry. While a student chaplain at the Trenton State Prison he met George De Los Santos, a prisoner serving a life sentence for murder. Convinced of his innocence, McCloskey took on De Los Santos's case. His efforts led to Dos Los Santos's exoneration and release from prison in 1983. In the same year McCloskey founded Centurion Ministries, the first non-profit organisation in the world dedicated to freeing individuals who are wrongfully incarcerated. Since then Centurion has been responsible for 70 releases of men and women serving life or death sentences for crimes they did not commit.

McCloskey's memoir, WHEN TRUTH IS ALL YOU HAVE, was published in 2020 with a Foreword from John Grisham.

He retired from Centurion in 2015