He was born on 22 October 1937 to Cypriot immigrants in Alexandria, Egypt. His parents came from the small village of Ayious Vavatsinias, in the district of Larnaca, Cyprus. Loizos moved to Athens at the age of 17 intending to study pharmacology but soon gave up his studies in order to concentrate on his musical career. He was a self-taught musician, with no formal musical arts training. His first recordings were made in 1963 but he started gaining a larger audience after 1967. By 1975 Loizos had become one of the most popular artists in Greek music.
He died on 17 September 1982 in a hospital in Moscow, Soviet Union after suffering several strokes. He was well known for his leftist political ideology and was an outspoken critic of the Greek military junta. He was also an active member of the Greek Communist Party. The year 2007 was declared "Manos Loizos Year" in Greece.