Early on, he began his literary activity in newspapers and magazines. In the 1920s, José Régio collaborated with the Porto magazines Crisálida and A Nossa Revista, as well as the Coimbra magazines Bizâncio and Tríptico. But it was in Coimbra that he consolidated his literary skills, as a result of his intense contact with the books that came to influence his work, as well as his contact with the intellectuals who marked one of the most fruitful periods of the 20th century, both in terms of literary creation and criticism.
The year after graduating, he published his first volume of poetry Poemas de Deus e do Diabo (Poems of God and the Devil), signing it with the literary pseudonym José Régio.
In March 1927, together with João Gaspar Simões and Branquinho da Fonseca, he founded the magazine Presença, which lasted thirteen years and was considered the magazine that publicised the “second modernism”.
After completing his studies, he began his teaching career, with a brief stint as a temporary teacher at the Alexandre Herculano High School in Porto, until he was appointed, in 1930, as a permanent teacher at the Portalegre High School, a position he held until he retired in 1962.
From then on, he lived alternately between Vila do Conde and Portalegre, until he settled permanently in Vila do Conde in 1966.
José Régio died on 22 December 1969 from heart disease.