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

In 1937 he moved to Thessaloniki, where he served his military service, and stayed there for about ten years, during the German occupation of Greece. There he became famous 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) and Prodromos Tsaousakis (Πρόδρομος Τσαουσάκης).

Tsitsanis died at the Royal Brompton Hospital in London following a lung operation, on his sixty - ninth birthday. He was mourned across Greece, where his music is still enjoyed to this day and he is regarded as a legend of rebetiko music.