By the end of the 15th century, many of those persecuted by the Inquisition in Castile took refuge in Portugal. The Jewish community or labeled as such was so numerous in the village in the sixteenth century that in the lists of those presented in Autos da fé held in Évora by the Inquisition, Campo Maior appears among the lands of the Alentejo with the highest number of defendants of Judaism.

The war with Castile from 1640 will produce the first major transformations with the need to fortify the village.

In the seventeenth century one in every four people residing in the village, was a military and the village became at that time the most important military center of the Alentejo, after Elvas.

The first years of the 19th century are in Campo Maior of great agitation. A siege in 1801 by the Spaniards and a local revolution in 1808 against the French who had then invaded Portugal.

The campomaiorense uprising against the Napoleonic occupation will be victorious due to the support of the Badajoz army that then remained in the village for about three years.

In 1811 a new French invasion arose which made a closed siege for a month to the village, forcing it to capitulate. But its resistance was such that allowed time for the British-Portuguese reinforcements to arrive under Beresford, who put the French in stampede.

The struggles between liberals and absolutists in Campo Maior are also remarkable events.

And in 1865, cholera killed, for about two and a half months, an average of two people a day.