Charles Church should never have been called Charles Church. The Plymouth that petitioned King Charles I in 1634 for a second parish was a Puritan town, sympathetic to the Pilgrim Fathers who had sailed from its harbour fourteen years earlier. The High Anglican king had no love for Plymouth's Presbyterian leanings, and he ignored the petition for seven years. Only in 1641 did he relent, and only after Robert Trelawny, the local MP with royalist sympathies, pressed him. The letters patent were signed on 21 April 1641, the Act of Parliament passed that summer. The king insisted on one condition: the new church would bear his name. Within two years, England was at war with itself, and Charles I would lose his head.

Construction began in 1641 and stopped almost immediately. Plymouth declared for Parliament and was besieged by Royalist forces from 1643 to 1646. The half-built church served as stabling for cavalry horses, and yet parts of it were still used for worship. A wedding is recorded on 10 May 1644. Baptisms began in January 1645. The first preaching minister, Francis Porter, was in place by 1643, sermonising in a roofless shell while cannonballs landed elsewhere in the town. A map of besieged Plymouth from 1643 shows the church marked but unroofed, a building under construction that refused to wait for the war to end. The church was finally consecrated on 2 September 1665, twenty-four years after the first stone was laid.

Robert Hawker became minister in 1784 and stayed for forty-three years. He was called 'the Star of the West' for sermons that could hold thousands rapt for an hour at a time. He was a bold Evangelical, prolific author, advocate for the parish poor, and beloved by his congregation in ways that outlasted him. When he died in 1827, his successor was not chosen from the obvious candidate, his own curate Septimus Courtney, and the congregation revolted. They built their own church for Courtney instead, the first of eight daughter churches that Charles would seed across Plymouth between 1829 and 1910. The Household of Faith Sunday school, founded at Charles in May 1784 with twenty children, may have been the first purpose-built Sunday school building in the world.

When the fires were out and the war was over, Plymouth had moved its population to the new suburbs. The city centre was rebuilt around the bones of the old. Charles Church stood at the heart of it: roofless, scorched, surrounded ten years later by the construction of a roundabout that turned the ruin into a traffic island. On a Saturday in 1958, the vicar J. Allen James dedicated the church as a living memorial to the civilians killed in the Plymouth Blitz. The commemorative plaque on the north wall has been replaced once since. In 2001 a service of reconciliation between Germany and Plymouth was held inside the roofless walls, with the German ambassador present. One parishioner, Miss Leigh, born in 1903 and a member of the church from birth, said the bombing of Charles in 1941 was one of the few things in her life that made her cry. 'My life seemed to be completely broken on that day.'