Saxe-Weissenfels (German: Sachsen-Weißenfels) was a duchy of the Holy Roman Empire from 1656/7 until 1746 with its residence at Weißenfels. Ruled by a cadet branch of the Albertine House of Wettin, the duchy passed to the Electorate of Saxony upon the extinction of the line.

John George I of Wettin, Saxon prince-elector from 1611 to 1656, had disposed in his testament that while his eldest son John George II would succeed him as elector, his younger brothers should be vested with secundogeniture duchies as an appanage. Therefore, upon his death the Duchies of Saxe-Zeitz, Saxe-Merseburg and Saxe-Weissenfels arose, the latter was granted to the second eldest son Augustus, who already served as the Protestant administrator of the Archbishopric of Magdeburg since 1638, then residing at Halle. From about 1660 he had the Baroque Neu-Augustusburg residence built at Weißenfels.

Beside Weißenfels the duchy comprised the ämter of Freyburg, Sachsenburg (present-day Oldisleben), Sangerhausen, Eckartsberga, Weißensee and Langensalza. Duke Augustus enlarged its territory by several lordships originally held by the Magdeburg archbishops and adjudicated to Saxony by the 1635 Peace of Prague, including the immediate lordship of Querfurt as well as the exclaves of Jüterbog, Dahme and Burg. By Querfurt, the ducal Saxe-Weissenfels line gained the status of an Imperial State (at times called Saxe-Querfurt) and member of the Upper Saxon Circle, though without a vote in the Reichstag. In 1659 Augustus also acquired the County of Barby, which upon his death in 1680 was granted to his younger son Heinrich. Augustus eldest son and successor Duke Johann Adolf I sold Burg to Brandenburg in 1687.