Popović was born in Werschetz (Vršac), in Habsburg Monarchy (Temesch County of Habsburg Kingdom of Hungary, modern Serbia).His father Šterija (Greek: asterion) was a Greek merchant, possibly of Aromanian origin. His maternal grandfather was known painter and poet Nikola Nešković, whom he would later write the biography of.

Popović attended grammar schools in Vršac, Karlowitz (Sremski Karlovci), Temeschwar (Timișoara) and Ofenpesth (Budapest). He studied law at Käsmark (Kežmarok). After he finished his studies (1830), he worked as a professor, and from 1835, when he passed his bar examination, he returned to his hometown where he first taught Latin, then opened his law practice. Like many other intellectuals of Vojvodina, driven by patriotic feelings, he decided to work in the Principality of Serbia. He began to write historical dramas but soon switched to comedy. In 1840 he went to Kragujevac to study at the pedagogic school of natural law. In the same year he, he moved to Belgrade, where he would spend eight years, teaching at what was then the most advanced school in Serbia, Grande École (Belgrade Higher School, future University).

He was instrumental in founding the Serbian Academy of Sciences and the National Museum. He continued to write dramas, which he also organized, staged, and directed. He was appointed head of the Ministry of Education by the constitutional government in 1842. He remained in this position until 1848, working on organizing the school system and education in Serbia. His continued disagreement with the leading politicians of the day and ill health would soon force him to withdraw from public life. At the beginning of the same year (1848) he decided to tender his resignation and return to Vršac (1848-9 part of Serbian Vojvodina, 1849-60 Serbia and Temeschwar), where he lived till his death in 1856, deeply disappointed with people and life in general. He is buried at the Orthodox cemetery in Vršac.