After receiving his PhD in 1942, Smith began teaching in the Chemistry Department at the Missouri School of Mines in Rolla. While teaching at Missouri, Smith became a mentor to a brilliant 15-year old high student and future National Medal of Science winner named M. Frederick Hawthorne who would eventually follow him to Pomona.
During World War II, Smith worked on the Manhattan Project at the Hanford Site in Richland, Washington. During the 1951–1952 academic year, he did a Guggenheim Fellowship in England on surface chemistry.
Smith joined the faculty at Pomona in 1945. His research focus was colloids. In 1956, he was promoted to the rank of full professor, and he later became the chair of the colleges chemistry department. During the 1958–1959 academic year, he did another fellowship in England sponsored by the American Chemical Societys Petroleum Research Fund.
In 1958, he co-authored with colleague W. Conway Pierce the textbook General Chemistry Problems. He and Pierce published several later editions of the book under the title Solving General Chemistry Problems.
Smith was an early adopter of computer technology, which he used in his courses.