The Phoenicians and Greeks had already settled in the bay of Lagos. The Carthaginians introduced wine and olive cultivation in the 4th century BC. The Roman name Lacobriga is the first known name of the settlement.

In 716 the Moors conquered Lagos. Under their rule, the city wall was renewed in the 10th century. In 1189, Dom Sancho I conquered Lagos, but three years later the Moors returned. It was not until 1241 that Dom Paio Peres Correia, with military support from German and English knightly orders, was finally able to wrest the city from the Moors.

In the 15th century, Lagos' port was the starting point for numerous African expeditions undertaken by Portugal under Henry the Navigator (Dom Henrique o Navegador). He made Lagos an important base for his fleet and had the caravel developed and built here from around 1440. This new type of ship was not only seaworthy, but was also able to sail close to the wind and tack against the prevailing wind direction.

From 1433 onwards, Gil Eanes set sail from Lagos several times, finally sailing beyond Cape Bojador for the first time. The cape was considered the border of the world at the time.

Another sailor, Rui de Sequeira, conquered a Benin fortress called Eko in what is now Nigeria in 1472. Today Lagos, formerly Eko, is with around 16 million inhabitants much better known worldwide than its godmother in Portugal. The African voyages of Portuguese ships brought black slaves from Guinea and Senegal to Europe for the first time in modern times. In 1444, Lagos received an important slave market. Human trafficking was not banned until 1820.

After the earthquake of 1755, a massive tidal wave eleven metres high devastated the city. Lagos was subsequently rebuilt and the city walls from that time still surround large parts of the old town today.

The church was originally called the "Church of Santo António dos Militares", as it was commissioned by the military. It was completed in 1707, destroyed in the earthquake of 1755 and rebuilt in 1769.