After obtaining her bachelor's degree, Calloway interned at the Johns Hopkins University Hospital as a dietician in 1944. The following year, she was a research nutritionist at the University of Illinois at Chicago medical school. At UIC, she researched how protein intake and exercise influenced the time people took to recover from surgery. Patients who ate sooner after surgery and had physical activity recovered faster than those who did not. From 1948–1951, she was a consulting nutritionist at the Medical Associates of Chicago. She then moved to the QM Food and Container Institute, where she was a nutritionist from 1951–1958, head of the metabolism lab from 1958–1959, and chief of the nutrition branch from 1959–1961. While at QM, she worked with the US Army to research the potential of foods to protect against dangerous radiation. She discovered that broccoli can have a protective effect against cancer caused by radiation. She also researched food irradiation and discovered that its effects on nutrient content were similar to heat processing. In 1961 she took a position at the Stanford Research Institute in the department of food science and nutrition, where she stayed until 1963. At Stanford, she created a freeze-dried orange juice product that eventually became Tang. She also worked on developing packaging for space food, gut microbiota, flatulence, and the potential of unicellular organisms as food. During the course of this research, Calloway discovered that lactose intolerance could be diagnosed by a breath test.
