Born in Matalana, a village in the south of Mozambique, Ngwenya spent his early life attending mission schools and helping his mother on the farm. At 12 he went to the city of Lourenzo Marques (now Maputo) to find work, becoming ball boy for a tennis club in 1953. This allowed him to resume his education, and he took classes at night, through which he developed an interest in art. Augusto Cabral, a member of the tennis club, gave him materials and helped him to sell his art.
In 1958 Ngwenya attended some functions of Nucleo de Arte, a local artists' organization, and received support from the painter Ze Julio. The next year he exhibited publicly for the first time, as part of a group show; two years later came his first solo exhibition, at the age of 25. In 1963 some of his poetry was published in the journal Black Orpheus, and his work was included in the anthology Modern Poetry from Africa.
In 1964 Ngwenya was detained by the PIDE, the Portuguese secret police, and spent 18 months in jail. He was given a grant from the Gulbenkian Foundation in 1971, and studied engraving and ceramics. Since 1981 he has worked full-time as an artist. His work has been shown throughout Africa, and is in the collection of the National Museum of African Art in Washington, DC. In addition, he has executed numerous murals, including for Frelimo and UNESCO. He has also helped to start a number of cultural institutions in Mozambique, and was a founder of the Mozambican Peace Movement.
Ngwenya has been awarded the Nachingwea Medal for Contribution to Mozambican Culture, and has been made a Grande Official da Ordem do Infante D. Henrique. In 1997 he was named a UNESCO Artist for Peace and received a Prince Claus Award.