Senica's history is closely related with the Branc castle, built in 1251-1261. It was first mentioned in 1256 and received its city privileges in 1396, confirmed in 1463 and 1492. The city was affected by Turkish wars, anti-Habsburg uprisings and reformation and counter-reformations in the 17th century. In 1746, it became seat of a district within the Nitra county.

A significant silk-producing company is based in Senica. The company was established in 1954 under the name "Slovensky hodváb". In 2005 the production of viscose rayon was halted. After the merger of Slovensky hodváb and Kord to the new company Slovkor, it continued only with the production of Synthetic fiber for technical purposes. In February 2014 the factory chimney, which dominated the city more than half century and was visible from long distance, was demolished.

OMS lighting, one of the biggest luminaire companies in East-Central Europe, is also based in Senica. With around 1000 employees and exporting 98% of its production to more than 100 countries, the company is a referent in the economy of Senica.