[6][7] Souza joined the Communist Party of India soon after, and co-founded the Bombay Progressive Artists' Group in 1947.

His success as an artist took off following the publication in 1955 of his autobiographical essay Nirvana of a Maggot in Stephen Spender's Encounter magazine.

[12] Souza's career developed steadily, and he participated in several shows, receiving positive reviews from John Berger.

According to Berger, Souza's style "was deliberately eclectic: essentially Expressionist in character", but "also drawing on the post-war Art Brut movement and elements of British Neo-romanticism".

[14] His painting Birth (1955) depicting his mistress Liselotte posing naked while pregnant with their first daughter Keren,[7] set a world auction record in 2008 for the most expensive "Indian" painting sold till then when it was purchased by Tina Ambani for US$2.5 million (Rs 11.3 crore) at a Christie's auction.

[17] Souza met a Goan fashion designer named Maria Figueiredo in 1945, they married soon after and had a daughter together.

[10] In 1954 Souza met Liselotte Kristian (also surnamed Kohn, 1919–1990), a married Jewish actress and Progressive League member, who became his mistress.

[24] Souza's eldest daughter by his partner Liselotte Kristian is the British-Israeli painter Karen (Keren) Souza-Kohn.

[13][18][25] Karen's son is the British-Israeli street artist Solomon Souza, known best for his murals in the Mahane Yehuda Market.