In 1776, Tyszkiewicz was an envoy to the Sejm from the Vilnius Voivodeship. and in 1778 was made the Marshal of the Sejm. In 1782, he was a supporter of the Permanent Council. During the Polish–Russian War of 1792, on a meeting of 23 July, he supported the accession of the king to the Targowica Confederation, whose example Tyszkiewicz himself soon followed, becoming Grand Marshal of Lithuania. During the Grodno Sejm, he was chosen as a negotiator with the Russian ambassador Jacob Sievers, and so on 22 July 1793 he signed the treaty of the cession of land to Russia, and then on 25 September to Prussia, as part of the Second Partition of Poland. In 1795, he was the leader of the Lithuanian party paying homage to Catherine II.