From 1127 ruled in Smolensk. Founder of the Smolensk princely dynasty. Turned the Smolensk land into one of the mightiest principalities, having kept it from fragmentation. In the 1120 s – 1140 s took part in campaigns against Polotsk princes and Lithuanians. Waged defensive wars against the Polovtsians, in battles with them used the Karakalpaks, Oguzes and other Turkic tribes. In 1144 and 1146 along with the Grand Prince of Kyiv Vsevolod II Olhovych waged a successful war against the Prince of Halych Volodymyrko Volodarovych.
In 1149–1150 supported his brother Iziaslav Mstyslavych in his struggle against Yuri Dolgoruky for the Kyivan throne. During the rule of Rostyslav Mstyslavych an irreversible disintegration of the Kyivan state into the number of separate principalities took place, and a separate eparchy was established in Smolensk (between 1133 and 1150). Saint Polikarp Pechersky, Archimandrite and Hegumen of the
In the spring of 1167, returning from the campaign against Novgorod, the Grand Prince went sick. He was persuaded to stay in Smolensk, where his son Roman reigned, but Rostyslav Mstyslavych decided to return to Kyiv.
Buried in St. Theodore’s Monastery in Kyiv. Beatified by the Orthodox Church.
His son Mstyslav Rostyslavych (died in 1180) took part in wars of the alliance of Old Rus princes against Andrei Bogoliubsky, and in 1173 successfully repulsed his brother Vsevolod’s attack on the town of Vyshgorod.