Born in Rosario, Argentina, to an Italian father, Fontana spent his formative years in Italy before returning to Argentina during World War II. He studied at the Accademia di Brera in Milan, where he later established himself as a pivotal figure in the development of post-war European abstraction.

Fontana is most recognized for his Concetto spaziale (Spatial Concept) series, which features monochromatic canvases punctured or sliced with a razor. These works challenged the traditional boundaries of painting by emphasizing the physical depth and the void behind the canvas. Beyond painting, he experimented with neon lighting and sculptural environments, notably for the Milan Triennale.

His legacy remains central to the history of 20th-century art, with his theoretical writings on Spatialism influencing generations of artists interested in the intersection of art, technology, and physical space.