Between 1513 and 1520 the mediaeval church was rebuilt by order of King Manuel I. The rebuilding was sponsored by the King but also by the local population and the Master of Santiago. The style was the Manueline, the Portuguese variation of late Gothic, as attested by the main and lateral portals of the present church, the sole survivors of the Manueline building. In 1531 a strong earthquake stroke Setúbal and the Church of São Julião was damaged; the building was considerably modified in Mannerist style and reinaugurated in 1570.
The original church was almost completely destroyed by the Great Earthquake of 1755 and was greatly rebuilt and redecorated in the last third of the 18th century following the late Baroque style. From this stage date the general appearance of the façade, the inner wooden roof, the painted tiles, the main and lateral altarpieces and the main chapel.
The nave of the church is divided in three aisles by arches built during the Mannerist repair works following the 1531 earthquake. After the 1755 earthquake the interior of the church was re-decorated in Baroque style, with gilded columns decorated in talha dourada (a typical Portuguese technique to decorate woodwork with gold leaves) in the choir and a beautiful altarpiece. The painting of the main altarpiece is a work by Pedro Alexandrino.
The side walls are decorated with 18th century blue-and-white azulejos (ceramic tiles), depicting scenes from the life of Julian and Basilissa.