After graduation from Amherst, Drew took on a position as a biology teacher at Morgan State University in Baltimore, Maryland and also served as the school’s Athletic Director. During his two years at Morgan State, he helped to turn the school’s basketball and football programs into collegiate champions.

In 1928, Charles decided to pursue his interest in medicine and enrolled at McGill University in Montreal, Canada. He was received as a member of the Medical Honorary Society and graduated in 1933 with Master of Surgery and Doctor of Medicine degrees, finishing second in his class of 127 students. He stayed in Montreal for a while as an intern at Montreal General Hospital and at the Royal Victoria Hospital. In 1935, he returned to the United States and began working as an instructor of pathology at Howard University in Washington, D.C. He was also a resident at Freedmen’s Hospital (the teaching hospital for Howard University) and was awarded the Rockefeller Foundation Research Fellowship.

He spent two years at Columbia University in New York attending classes and working as a resident at the Columbia University Presbyterian Hospital. During this time he became involved in research on blood and blood transfusions. Years back, while a student at McGill, he had saved a man by giving him a blood transfusion and had studied under Dr. John Beattie, an instructor of anatomy who was intensely interested in blood transfusions.

Now at Columbia, he wrote a dissertation on “Banked Blood” in which he described a technique he developed for the long-term preservation of blood plasma. Prior to his discovery, blood could not be stored for more than two days because of the rapid breakdown of red blood cells. Drew had discovered that by separating the plasma (the liquid part of blood) from the whole blood (in which the red blood cells exist) and then refrigerating them separately, they could be combined up to a week later for a blood transfusion. He also discovered that while everyone has a certain type of blood (A, B, AB, or O) and thus are prevented from receiving a full blood transfusion from someone with different blood, everyone has the same type of plasma. Thus, in certain cases where a whole blood transfusion is not necessary, it was sufficient to give a plasma transfusion which could be administered to anyone, regardless of their blood type. He convinced Columbia University to establish a blood bank and soon was asked to go to England to help set up that country’s first blood bank. Drew became the first Black to receive a Doctor of Medical Science degree from Columbia and was now gaining a reputation worldwide.

On September 29, 1939, Charles married Lenore Robbins, with whom he would have four children. At the same time, however, World War II was breaking out in Europe. Drew was named the Supervisor of the Blood Transfusion Association for New York City and oversaw its efforts towards providing plasma to the British Blood Bank. He was later named a project director for the American Red Cross but soon resigned his post after the United States War Department issued a directive that blood taken from White donors should be segregated from that of Black donors.