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The foundation of Vejano is attributed to the inhabitants of the Etruscan city of Veii, destroyed by the Romans in 396 BC. The area is located at the confluence of two rivers, Crovino and Mignone, where the Romans built a large villa and there were also spas.

The medieval town was founded on a hill around a castle during the period of the Barbarian invasions, and assumed its present appearance around the thirteenth century.

After being dominated by the Prefects of Vico and by the Anguillara, in 1465 it became a possession of the Church entrusted to families Della Rovere, Orsini and Santacroce. They held it for almost two centuries from 1493 to 1664, and with them came the period of development in the early sixteenth century. The family encouraged important projects in construction and agriculture, and introduced into the area crops of ​​the New World such as potatoes and tomatoes.

The last representative of Santacroce, George III, was beheaded in Rome in 1664 after being accused of matricide. In 1670 the Vejano passed into the hands of Altieri who remained for three centuries until the extinction of the main branch of the family. Today the castle is owned by Francesco di Napoli Rampolla.

The town suffered from heavy bombardment in World War II.