Cowbridge church was first built sometime in the 13th century, probably soon after the granting of a charter to Cowbridge borough in 1254. It was built as a chapel of ease to Llanblethian. The original church consisted of nave, chancel, and the massive tower which survives unchanged. Internally, the church underwent many changes over succeeding centuries. The south (or Llanquian) aisle was added to the nave in 1473 to provide for Llanquian worshippers whose chapel (near Aberthin) was ruinous. This south aisle was reputedly built by Lady Anne Neville the wife of the lord of Glamorgan, Richard Duke of Gloucester (the future Richard III). In 1484 Richard III granted a chaplaincy to Holy Cross church. A chantry chapel (now the vestry) served by a chantry priest was added to the building in the 15th century.
The close association between the old Cowbridge Grammar School, Jesus College Oxford and the church is recorded in memorials to former headmasters of the school, and by inscriptions, dedications and coats of arms in stained glass windows.