Hendrick de Keyser, who would later design the Noorderkerk and Westerkerk in Amsterdam, designed a pseudo-basilica, with a nave and two lower aisles. The north and south facades are decorated in the so-called Amsterdam Renaissance style, a style very characteristic for the work of De Keyser. After his death in 1621, he was burried in the Zuiderkerk.
In the last four centuries the church has been modified several times. At the end of the seventeenth century the original stained-glass windows were replaced by plain glass to improve the way the light falls into the building.
The last church services in the Zuiderkerk were held in 1929. Since then, the church has had many different functions. The church was used as a storage space for Bibles and during the winter of 1944-45 the church served as a morgue. In 1968 the church became property of the municipality of Amsterdam. The church was closed for a while because of its ruinous state.
A rigourous restauration took place between 1976 and 1979. Since 1988, the Zuiderkerk has been in use as a municipal information centre for urban development and housing.