Gregg Semenza was born in New York City. After studying medical genetics at Harvard University, he pursued doctoral studies at the University of Pennsylvania in Philadelphia, receiving his doctorate there in 1984. After completing his pediatric training, he began working at Johns Hopkins University in Baltimore, Maryland, where he is still active.

Animals need oxygen for the conversion of food into useful energy. The importance of oxygen has been understood for centuries, but how cells adapt to changes in levels of oxygen has long been unknown. William Kaelin, Peter Ratcliffe, and Gregg Semenza discovered how cells can sense and adapt to changing oxygen availability. During the 1990s they identified a molecular machinery that regulates the activity of genes in response to varying levels of oxygen. The discoveries may lead to new treatments of anemia, cancer and many other diseases.