The town lies at the confluence of the Lužnice River and Kozský Creek and is a part of the Tábor industrial agglomeration. The town is first mentioned in a document of 1262. The original settlement gradually turned into an economic center whose growth was further accelerated by the silver ore mines.

At the turn of the 14th and 15th century the town was a flourishing town of crafts and the cradle of the Hussite movement. The Hussites of Sezimovo Ústí destroyed the settlement in 1420 and moved to the newly founded town of Tábor. The original settlement was not renewed until 1828. In 1939 the site of the former municipal courtyard was replaced with Sezimovo Ústí II, where the MAS (later Kovosvit), a large industrial plant, was built and later neighbored a small town which adjoined Sezimovo Ústí I. At the outskirts of Sezimovo Ústí I, in the middle of a vast natural park one can admire the villa of Dr. Edvard Beneš, the second president of Czechoslovakia, who would often stay there and who also passed away there. In May 2005, the Dr. Edvard Beneš Memorial was set up in the park near the villa and commemorates the work of Beneš as a statesman, his democratic legacy as well as his family life. The park also conceals the Vault of the Beneš' family, which is freely accessible.