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Marco Sassone was born in Campi Bisenzio, a Tuscan village, in 1942. The family moved to Florence in 1954, and there he met painters Ottone Rosai and Ugo Maturo, who encouraged him to follow his interest in art. In 1959 he enrolled at the Istituto Galileo Galilei, where he studied architectural drafting for several years. In 1963 he studied with painter Silvio Loffredo, a professor of art at the Accademia in Florence, himself a pupil of the Austrian master Oskar Kokoschka.

In November 1967, soon after the flood had devastated his city, Sassone moved to California. He exhibited for the first time in the United States at the Dalzell-Hatfield Galleries in Los Angeles and became a regular exhibitor at the annual Festival of the Arts in Laguna Beach.

Throughout the seventies, he exhibited extensively in the U.S. and abroad. In 1976 he collaborated with director John Wilson to produce an autobiographical documentary. The following year his work was exhibited at the National Academy of Design in New York. Marco Sassone received a gold medal in 1978 from the Italian Academy of Arts, Literature and Science. In 1979 the monograph Sassone by art historian Donelson Hoopes was published in concurrence with the artist's exhibition at the Laguna Art Museum.

In 1981 Sassone moved his studio to San Francisco. During the 80's his exhibition schedule continued along with his numerous lectures. In 1982 Marco Sassone was knighted by the president of Italy, Sandro Pertini, into the "Order to the Merit of the Italian Republic". In 1987 Sassone received a commendation for his "contribution to the community through his art" from the City of Los Angeles. The following year his solo exhibition was mounted at the L.A. Municipal Art Gallery.

By the late eighties, the artist had become increasingly concerned with social themes. He began extensive and personal research on the homeless and painted a series of large canvasses and charcoal drawings portraying the life he observed on the streets. A number of these works were exhibited at the Chicago International Art Exposition, the Basel Art Fair in Switzerland, Body Politic at the San Francisco Arts Commission Gallery and Issue of Choice at the Los Angeles Contemporary Exhibition.

In March of 1994, his exhibition titled Home on the Streets opened at the Museo ItaloAmericano in San Francisco, later traveling to Los Angeles in 1996 and Florence, Italy in 1997.

In 2003, the Cloisters of Sant' Agostino Museum in Pietrasanta, Italy mounted the show "Master and Pupil" with works by Marco Sassone, Silvio Loffredo and Oskar Kokoschka, and a catalogue authored by Peter Selz.

In 2005 Marco Sassone relocated his studio to Toronto, Canada and immediately forged a rapport with the city. His profound interest in the urban landscape resulted in a series of large canvases that were exhibited at the National Shrine of St. Francis, San Francisco; Palazzo dell 'Informazione, Rome, Italy and the David Findlay Jr. Fine Art, New York.