The congregation was formed in 1841,[1] as a part of the United Presbyterian Church of Scotland's Canadian Synod, and had been served monthly since 1837 from nearby West Flamboro by the UPC's pioneer missionary to the region, Thomas Christie.

On June 21, 1906, the 1858 building was destroyed in a massive fire, and plans were commenced to rebuild in a new location; the minister's son, John M. Lyle, was architect of the new building, which was opened on June 14, 1908, complemented with a large Casavant Frères pipe organ.

Nevertheless, the church's interior is dominated by a series of traditional stained-glass windows portraying episodes from the Bible.

Central's spire, which is illuminated at night, is a distinctive landmark visible throughout the surrounding neighbourhoods, as well as from the top of the nearby Niagara Escarpment.

The congregation remains active in downtown Hamilton, until recently known for its music programme, and its connection with The Argyll and Sutherland Highlanders, as well as its reputation for lengthy pastorates.