The Presbyterian Church of Nigeria was founded by the United Presbyterian Church of Scotland missionaries led by the Rev. Hope Masterson Waddell on the invitation of King Eyo Honesty II and King Eyamba V.

The missionaries arrived in Calabar and founded the first Presbyterian church at Creek Town in 1846. From Calabar, the church began to grow. In 1858 the Presbytery of Biafra was formed. The Synod of Biafra formed in 1921.