Sieniawa was founded in the area which was covered by the village of Dybków. The Sieniawski family wanted to make it main administrative center of their estates. In ca. 1650, a brick fortress was built on a hill near contemporary Sieniawa. In the following years, the Sieniawski family built their manor house near the fortress, and began construction of the town, together with the San river port. A Dominican church and abbey was built, and in the 1660s, walls were built, to protect Sieniawa from Crimean Tatars raids. Mikolaj Hieronim Sieniawski, the founder of the town, died at the age of 39, but his son Adam Mikolaj Sieniawski continued the work of his father, and invested heavily in Sieniawa. In 1731, Adam's daughter Maria Zofia married Prince August Aleksander Czartoryski, and Sieniawa became property of the Czartoryski family.
Until 1772, Sieniawa remained an important river port and a defensive establishment. Following the Partitions of Poland, the situation changed, and fortifications were not needed any longer. Since the new Austrian - Russian border was north of Sieniawa, the San lost its function of a waterway, and the town stagnated as part of Austrian Galicia. In 1855, Sieniawa belonged to the District of Przemyśl. The town remained property of the Czartoryski family, and was famous across Galicia for its bricklayers.
In May 1915 Sieniawa was almost completely destroyed, and in November 1918 the town became part of Second Polish Republic’s Lwów Voivodeship. In the interwar period, Sieniawa's population declined, and unemployment was high, which resulted in street fights and demonstrations.