It became a part of the Grand Duchy of Lithuania in the 14th century (soon part of the Polish–Lithuanian union), and Grand Duke Algirdas rebuilt it as a defensive stronghold against Muscovites and Tatars.

In 1535, it was besieged and captured by Polish-Lithuanian forces and the defenders were executed however, it soon fell back to Muscovy.

[10] In 1648, during the Khmelnytskyi Uprising, Zaporozhian Cossacks seized the town, and 188 families of local Ruthenian nobility recognized the Cossack hetman as a new governor,[11] within the Polish–Lithuanian Commonwealth, after which the Ukrainians staged a anti-Jewish pogrom.

[10] Starodub remained rudiments of Cossack Hetmanate's administrative division until 1782 when it became an uyezd town.

The Germans operated a Nazi prison and a forced labour battalion for Jews in the town.

As a significant center of the Cossack Hetmanate, Starodub is the only place in Russia where authentic examples of Ukrainian Baroque may be seen.

The Nativity Cathedral, built in 1617 and overhauled after a conflagration in 1677, is a typical example of Cossack Baroque.