He was close collaborator of Egas Moniz, Nobel prize of physiology, and wife Margarida da Beira Cardoso de Melo Machado, daughter of Joaquim José Machado, 70th, 82nd and 91st Governor of Mozambique and 110th Governor of Portuguese India, and wife Mariana Cardoso de Melo. His paternal great-grandfather was an illegitimate son of Bernardo António de Brito Antunes, 1st Viscount of Nazaré. His brother is neurosurgeon João Lobo Antunes.

At the age of seven he decided to be a writer, but when he was 16, his father sent him to the medical school of the University of Lisbon. He graduated as a medical doctor, later specializing in psychiatry. During this time he never stopped writing.

By the end of his education, Lobo Antunes had to serve with the Portuguese Army to take part in the Portuguese Colonial War (1961–1974). In a military hospital in Angola he became interested in the subjects of death and "the other."[1]

Lobo Antunes came back from Africa in 1973. The Angolan war for independence was the subject of many of his novels. He worked many months in the Germany and Belgium.

In 1979, Lobo Antunes published his first novel, Memória de Elefante (Elephant's Memory), in which he told the story of his separation. Due to the success of his first novel, Lobo Antunes decided to devote his evenings to writing. He has been practicing psychiatry as well, mainly at the outpatients' unit at the Hospital Miguel Bombarda of Lisbon.

His style is considered to be very dense, heavily influenced by William Faulkner and Louis-Ferdinand Céline, and his books are also very large in size.

He is also a supporter of Iberian Federalism.

He was granted the Grand Cross of the Order of Saint James of the Sword.