Born in Rimini, Italy to Rolando Prat and Evelina Genero, Hugo Pratt spent most of his childhood in Venice in a very cosmopolitan family environment. He was also related to actor Boris Karloff (né William Henry Pratt).
In 1937, Pratt moved with his mother to Abyssinia (Ethiopia), joining his father who had moved there following the conquest of that country by Italy. Pratt's father was captured in 1941 by British troops and, in late 1942, died from disease as a prisoner of war. The same year, Hugo Pratt and his mother were interned in a prison camp at Dirédaoua, and later was sent back to Italy by the Red Cross.
After the war, Pratt moved to Venice where he organized entertainment for the Allied troops. Later Pratt joined the 'Venice Group' with other Italian cartoonists, including Alberto Ongaro and Mario Faustinelli. Their magazine Asso di Picche, launched in 1945, concentrated on adventure comics. The magazine scored some success and published works by young talents, including Dino Battaglia. His eponymous character Asso di Picche (Ace of Spades) was a success, mainly in Argentina, where Pratt was invited in 1949.
In the late 1940s, he moved to Buenos Aires where he worked for Argentine publisher Editorial Abril and met Argentine comics artists like Alberto Breccia and Solano López. The passage to Editorial Frontera saw the publication of some of his most important early series. These included Sgt. Kirk and Ernie Pike, written by Héctor Germán Oesterheld.
Pratt taught drawing in the Escuela Panamericana de Arte directed by Enrique Lipszyc. During that period he produced his first comic book as a complete author, both writing and illustrating Anna nella jungla, which was followed by the similar Capitan Cormorant and Wheeling. The latter was completed after his return to Italy.
From the summer of 1959 to the summer of 1960, Pratt lived in London where he drew a series of war comics for Fleetway Publications, with British scriptwriters. He then returned to Argentina, despite the harsh economic times there. He moved again to Italy in 1962 where he started a collaboration with the children's comic book magazine Il Corriere dei Piccoli, for which he adapted several classics of adventure literature, including Treasure Island and Kidnapped by Robert Louis Stevenson.
In 1967, Pratt met Florenzo Ivaldi; the two created a comics magazine named after his character, Il Sergente Kirk, the hero first written by Héctor Oesterheld. In the first issue, Pratt's most famous story was published: Una ballata del mare salato, which introduced his best known character, Corto Maltese.
Corto's series continued three years later in the French magazine Pif gadget. Many of his stories are placed in real historical eras and deal with real events. Many of the minor characters cross over into other stories in a way that places all of Pratt’s stories into the same continuum.
Pratt's main series in the second part of his career include Gli scorpioni del deserto and Jesuit Joe. He also wrote stories for his friend and pupil Milo Manara for Tutto ricominciò con un'estate indiana and El Gaucho.
From 1970 to 1984, Pratt lived mainly in France where Corto Maltese, a psychologically very complex character resulting from the travel experiences and the endless inventive capacity of his author, became the main character of a comics series. Initially published from 1970 to 1973 by the magazine Pif gadget, it brought him much popular and critical success. Later published in album format, this series was eventually translated into fifteen languages.
From 1984 to 1995 Pratt lived in Switzerland where the international success that Corto Maltese sparked continued to grow. He died of bowel cancer on 20 August 1995.