He was born the sixth child of Stanisław Poniatowski, a Polish noble, and his wife, Princess Konstancja Czartoryska. After a careful education he traveled in western Europe as a young man. In 1757 he was sent by his mother's enormously powerful family to St. Petersburg to obtain Russian support for their plan to dethrone the Polish king Augustus III. While at the Russian court, he apparently did little for the family's interests but succeeded in becoming the lover of the future empress, Catherine II.

Poland at this time was in a period of steady decline, and, following the death of Augustus III in 1763, Catherine sought to ensure that the situation continued. Seeing the young Poniatowski as a convenient pawn, she used Russian troops and Russian influence to ensure his election as Stanisław II on Sept. 7, 1764. After coming to the throne Stanisław sought to bolster his royal power, improve the administration of government, and strengthen the parliamentary system. These reforms were opposed by some Polish nobles and by Catherine, who threatened to have him deposed. The reforms were dropped, and Catherine then interfered in Poland even further by pressing for full rights for non-Catholic religious dissenters. A revolt by Roman Catholics followed in 1768 and was not fully suppressed for four years. Its effect was to make Stanisław even more dependent on Russian support.

In 1772 Russia, Prussia, and Austria each annexed portions of Polish territory, despite Stanisław's appeals to the Western powers. In the years following this partition, Stanisław saw his own personal power cut away and limited by the manipulations of the partitioning powers. Fighting back, he succeeded in strengthening his position and achieved a full reform of Polish education. A more basic requirement to prevent further national decay was constitutional reform; after long and arduous debate, the Sejm (Diet) finally approved a new constitution on May 3, 1791. To oppose this constitution, the Confederation of Targowica was formed by a group of Polish nobles with Russian backing. In a subsequent invasion by Russia, despite valiant efforts by a small Polish army, the Russians succeeded in crushing the movement for a new constitution.

Stanisław was then forced to participate in the Russian-controlled Sejm at Grodno in 1793, which agreed to the second partitioning of Poland, this time between Russia and Prussia. The response was a Polish insurrection in 1794, during which Tadeusz Kościuszko overrode all royal authority. After the Russians had crushed the uprising, Stanisław abdicated on Nov. 25, 1795, as Poland was being partitioned again by Russia, Prussia, and Austria, the three countries this time annexing its entire territory. He died in semicaptivity at St. Petersburg. His two-volume Mémoires was published by S.M. Goryaninov (1914–24).