In 2002, James Ransone co-starred in the Harmony Korine drama film Ken Park as Tate. He starred as Ziggy Sobotka in The Wire
In 2010, he was cast in a recurring role in the HBO comedy series How to Make It in America, and the following year, appeared in a recurring role in the HBO drama series Treme. In 2012, he starred in the Sean S. Baker drama film Starlet.The following year, he starred in the AMC drama series Low Winter Sun as Damon Callis.
Ransone then went on to star in the 2012 horror film Sinister in the supporting role of Deputy So-and-So. In June 2014, Ransone joined the cast of Ti West's Western film In a Valley of Violence. In 2015, he had a co-starring role in the comedy-drama film Tangerine, reuniting him with director Sean S. Baker. Following the success of Sinister, Ransone returned to appear in the 2015 sequel Sinister 2, reprising his role from the first film but now as the main character. In 2016, Ransone starred in the Amazon Studios police procedural drama series Bosch as Eddie Arceneaux. In 2019, Ransone played Eddie Kaspbrak (sharing the role with Jack Dylan Grazer) in the supernatural horror film It Chapter Two.
