Displaying an inclination for painting from a very early age, he came to Athens in 1921 where until 1926 he studied at the School of Fine Arts, first under Alexandros Kaloudis and then Nikolaos Lytras. In 1930 he won the Benakeio Prize for his drawings for the wall paintings of the Ayios Dionysios Areopagitis and with that money made his first extensive educational tour of Europe, completing the illustration of the church walls from 1936 to 1939.

He began to exhibit in 1926, holding his first solo exhibition in 1929 at the Stratigopoulos gallery. A founding member of the “Techni” (Art) Group and “Stathmi” (Level), he contributed to their exhibitions as well as to the Biennales of Venice, in 1934 and 1964, Alexandria in 1957 and Sao Paolo in 1959. In 1955 the icons he made for the church of St. Constantine in Detroit were presented a that city’s Art Institute and in 1960 his work Lights and Shadows was exhibited at the Guggenheim Museum and awarded the local prize of the Greek Division of AICA. In 1975 and in 1983 his work was presented in exhibitions at the National Gallery.

For many years he taught at private and theater schools. In 1927 he began his involvement with set design, making the sets for many plays in both private and state theaters, as well as for quite a number of films. During the German occupation, he turned to engraving and circulated woodcuts, illustrated manuscripts and editions in manuscript, all clandestinely. His artistic creation also included book illustration, along with the publication of texts and caricatures in newspapers and magazines while in 1933, in collaboration with Agenor Asteriadis, he published “Pedika shedia” (Children’s Drawings).

A leading force of the “Thirties Generation”, Spyros Vasileiou was imbued with the ideal of “Greekness”. Using oils, tempera and water colors he depicted natural and urban space, portraits, still lifes and scenes from everyday life, combining select elements of tradition with models taken from constructivism, surrealism, pop art and photo-realism and creating compositions which were lyrical and, frequently, dream-like.