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Carlos Alfonzo attended the Academia de San Alejandro and University of Havana in Cuba. His work rapidly achieved recognition in the island, and it was acquired by the Museo Nacional de Bellas Artes. In 1977, the museum presented the exhibition Experimentos de Carlos Jose Alfonzo.

Alfonzo was part of the iconic 1979 exhibition Pintura Fresca (Fresh Paint, Cienfuegos Art Gallery), widely regarded as the precursor to the groundbreaking 1981 Volumen Uno (Volume One).

At the time Alfonzo left Cuba in 1980, the University of Havana was working on an exhibition of his work, which immediately was suspended. The essay for the catalogue, by Gerardo Mosquera, was never published. The name of Carlos Alfonzo was erased from the list of Cuban artists. Scorned as a dissident and a homosexual, in his last days in Havana, when he was under house arrest, he created murals - now vanished - on the walls of his home; a defense against not only a ruthless outside world but his own anguish. Alfonzo's works was also a personal search for harmony, beauty, and reconciliation.

Once in Miami, Alfonzo reconfigured his personal universe into the particular symbiosis that would distinguish his mature work. Symbols from many sources - Afro-Cuban, Catholic, Rosicrucian, tarot, and more - came together to unquiet harmony, battling for existence. His work evolved also to the focus on the body, especially the head, which he chopped off at neck level in clear reference to the Santeria, but most importantly as an expression of his inner world, progressively darker.

The news brought by his mother in 1990 about his father's death weakened him but that did not stop him to produce perhaps his most important works.

Carlos Alfonzo's works on the topic of AIDS first came to attention in the 1980's, when the disease became a global pandemic. It was featured in different exhibitions and magazines; becoming an important reference on the subject.

Alfonoz's work was marked by the experiment, on different materials, such as crumpled cardboard, cloth sacking, and newspapers, and for a passion for literature that prompted him to incorporate handwriting into his art. Darker colors, strong contrast and multiple symbols made of Alonzo's work a true representation oh his state of mind and inner universe, translated onto the canvas.

In 1990, the magazine Art News listed Alfonzo as one of the "ten artist to watch" in the 90's. In 1991, soon after his death, his work was included in the Whitney Biennial.