Founded by William Paul Quinn and Augustus Turner in 1836, the church was first known as Indianapolis Station. The first meetings were held in Quinn's log cabin. In 1841, a modest house of worship was constructed. The congregation had grown to 100 by 1848 and became active in the antislavery movement. The congregation supported the Underground Railroad, providing protection to slaves en route to Canada.
That black population made up approximately less than 3 percent of the total population in Indianapolis before the Civil War. Out of the total population of 1,338,710 in the state of Indiana in 1860, only 11,428 were African American. As the Civil War continued, the number of African Americans coming to Indianapolis from the South as well as rural areas around the state grew. The congregation's vocal support of the abolitionist movement led to a racially-motivated crime, as an arsonist destroyed the church in 1864. The congregation rebuilt the church in 1867.
Bethel AME Church members purchased a lot on West Vermont Street in 1867 for the construction of a new church building. By 1869 members had approved the name Bethel and moved to the new building here. The new place of worship also became a place for social activism as well as a venue for organizing and implementing services in the black community. Those services included providing money, clothing, and temporary lodging to African Americans immigrating to the city from the South after the Civil War.
Bethel AME Church continued to be an important thread in the fabric of the black community located to the northwest of Indianapolis's downtown area during the twentieth century, functioning as a space of racial solidarity and fulfilling a role that was interwoven throughout civil rights struggles and community outreach services for African Americans in the city. The church also served as a venue for the organization of local associations that were instrumental in the push to achieve better housing, education, and equal rights for African Americans. Both the Indianapolis NAACP chapter and Indiana State Federation of Colored Woman's Clubs were established at Bethel.
Members renovated the church building and adjoining parsonage in 1974 in order to make more space for outreach activities. Bethel AME Church was listed on the National Register of Historic Places in 1991. It is the only African-American church building in Indianapolis to receive that recognition.
Indianapolis's oldest African-American church is still active, occupying the same site it did in 1869. However, due to money issues and failure in fundraising, the congregation will soon move to a new building whilst the lot has been sold to a hotel development company. As of now, what will happen to the 1869 building is unknown. The state Historical Marker for Bethel AME Church, which is located across from the building on West Vermont Street, was dedicated on Saturday, June 20, 2009. The church is also a member of the Indianapolis Congregation Action Network (IndyCan) and has served as headquarters for IndyCan's Mass Transit Campaign since 2013.