She was born in Fajardo, Puerto Rico on August 23, 1944. degree from the University of Puerto Rico at Rio Piedras in 1965. In 1970, she received her M.D. degree from the University of Puerto Rico School of Medicine at San Juan. Novella then completed her internship and residency in nephrology at the University of Michigan medical Center in Ann Arbor. She 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. She was in private practice in pediatrics in Springfield, Virginia from 1976 to 1978.
In 1978, Novello joined the Public Health Service Commissioned Corps. Her first assignment was as a project officer at the National Institute of Arthritis, Metabolism and Digestive Diseases of the National Institutes of Health (NIH). She held various positions at NIH, rising to the job of Deputy Director of the National Institute of Child Health and Human Development (NICHD) in 1986. From September 1987, she served as Coordinator for AIDS Research for NICHD. She developed a particular interest in pediatric AIDS in this role.
During her years at NIH, Novello earned an M.P. H. degree from the John Hopkins School of Hygiene and Public Health in 1982. She also held a clinical appointment in pediatrics at Georgetown University Hospital from 1976. Novello also made major contributions to the drafting and enactment of the organ Transplantation Procurement Act of 1984 while assigned to the Senate Committee on labor and Human Resources.
Antonia Novello was appointed Surgeon General by President Bush, beginning her tenure on March 9, 1990. She was the first Hispanic and first woman to hold this position. .
During Her tenure as Surgeon General, Novello focused her attention on the health of children, women, and minorities, as well as on the smoking, underage drinking, and AIDS.