He was born Grigoris Dikaios in Poliani, Messinia prefecture, in 1788. As a young man, Papaflessas was educated in Dimitsana, Arcadia and became a monk. He was forced to leave Peloponnesus after a land dispute with a Turkish official. It is said, that as he was leaving, he swore vengeance against those who he thought had short-changed him.
Papaflessas took up residence in Constantinople where he was ordained a priest. On June 21, 1818, he was initiated into the Friendly Society (Filiki Eteria) by Panayiotis Anagnostou who would go down in history as "Anagnostaras". Papaflessas undertook the task of preparing the ground for the upcoming revolution against the Ottoman Empire in Moldavia and Wallachia. When he returned, he was sent back to Peloponnesus to prepare the locals for the revolt.
Papaflessas' task was not easy: many Greek officials preferred a peaceful co-existance with the Turks and shunned him so Papaflessas took his message to the common people. He was successful in enlisting many that he would lead when the Greek Revolution broke out on March 25, 1821.
Papaflessas took part in many battles of the revolution and helped halt the attempted invasion of the Peloponnese by Omer Vrioni. He also was involved in the Revolutionary Government taking part in the 2nd National Council and assuming the post of Foreign Minister. His position in government brought him in opposition to his friend and fellow revolutionary, Theodoros Kolokotronis, in the Civil strife that broke out during the war, however, when the Government jailed Kolokotronis, Papaflessas spoke out in favour of releasing him.
In 1825, the revolutionary war was threatened by the coming of Ibrahim pasha from Egypt. Papaflessas took a force of 1,500 men to defend Maniaki in Messinia. When Ibrahim's forces surrounded the Greek positions, most of Papaflessas' men escaped. The former priest was left with 500 men to face 3,000 better-equiped Egyptians but refused to retreat. On May 20, 1825, in the ensuing battle, Papaflessas fell alongside his men. It is said that after the battle, Ibrahim pasha ordered his men to find Papaflessas' body, had them wash it and lean it against a tree. Then, in admiration, the Egyptian pasha exclaimed "Now, there's a true man!".