Born on August 23, 1944, in Fajardo, Puerto Rico, Antonia C. Novello was the first of three children of the Coellos. Shortly after the birth of their daughter, the Coellos were informed that Antonia suffered from congenital megacolon, an abnormality of the large intestine. This required periodic visits to the hospital for treatment, because of her body's incapability to get rid of waste. Her father died at the age of 8 and shortly after her mother was told that Antonia could have an operation to fix the procedure yet it never happened.
Antonia received her B.S. degree from the University of Puerto Rico at Rio Piedras in 1965 and her M.D. degree from the University of Puerto Rico School of Medicine at San Juan in 1970. She then completed her internship and residency in nephrology at the University of Michigan Medical Center in Ann Arbor, Michigan. Antonia remained at Michigan in 1973-1974 on a fellowship in the Department of Internal Medicine, and spent the following year on a fellowship in the Department of Pediatrics at Georgetown University. From 1976 to 1978, she was in private practice in pediatrics in Springfield, Virginia.
Antonia Novello studied medicine and became a deputy director with the National Institutes of Health. In 1990, she was appointed by President George H.W. Bush as the first female and Latin U.S. surgeon general. She focused on publicizing the dangers of smoking and teenage drinking, expanding AIDS education, and improving health care for women, minorities, and children. She later worked for UNICEF and New York State.