St. James AME Zion, built in 1833, is believed to be the oldest church structure in Ithaca and one of the first of the AME Zion churches in the country.

An Underground Railroad station, St. James is located in a community that was an important transfer point for fugitive slaves en route to Canada. Many of these slaves, impressed by the support of the local community, decided to stay in Ithaca and constructed homes in the area surrounding St. James. The congregation officially expressed its anti-slavery sentiments through the writings and preaching of its pastors such as Thomas James who was known to have provided assistance to fugitive slaves. Famous leaders in the Underground Railroad are associated with St. James. Harriet Tubman, who played an active role in AME Zion church affairs in central and west New York, often visited St. James. Frederick Douglass is documented as visiting the church in 1852. Jermain Loguen, an active participant in the Underground Railroad was St. James third minister.