Born in Jerusalem, and later settled in Beirut with his family in 1939. He started his artistic career in 1942 at the Yarkon Studio. In 1957, he received a scholarship to study at the Academy of Fine Arts in Florence. In 1961-1962, he spent a year studying and painting in Paris. The rest of his life was spent living and painting in Beirut. Upon his death in 1993, Guiragossian received a state funeral.
Guiragossian had a foreboding sense of tragedy from his earliest years. Some of his early paintings were haunted by a figure who had lost one leg, a prophecy of his own misfortune, when in the early 1970s he lost a leg in an elevator accident.
Paul Guiragossian was consumed by his art and paid little attention to anything but his family and his painting. His mature works express the complexities of the human condition through renderings of vertical, elongated, purged bodies, both static and in motion, painted with thick layers of often luminous colors. His paintings are always serious in feeling. He also created frescoes, mosaics, stained glass windows, sculptures, and illustrations for books.