Tsitsanis was born in Trikala. From a young age, Tsitsanis was interested in music and learned to play violin, mandola and mandolin which were mainstays of so many of his songs. In 1936, he left for Athens to study law, and by 1937 had also learned bouzouki and made his first musical recording.

In 1938, he moved to Thessaloniki, where he completed his military service, and stayed there for about ten years, during the German occupation of Greece. There he became famous, opened also an ouzeri, got married and wrote many of his best songs that were later recorded after the end of the War. By the shut-down of the record companies by the German occupation Forces in 1941, he had already recorded about 100 of his own songs and played on many recordings of other composers.

In 1946, Tsitsanis returned to Athens and began recording many of his own compositions that made famous many of the singers that worked with him, such as Sotiria Bellou (Σωτηρία Μπέλου), Marika Ninou (Μαρίκα Νίνου), Ioanna Georgakopoulou and Prodromos Tsaousakis. Tsitsanis developed the “westernization” of the rebetiko and made it more known to large sections of the population, setting also the bases for the future laiko.