In 1937, Thompson was hired as a secretary for T. Leslie Shear, the Director of Excavations at the Athenian Agora.
Her responsibilities involved cleaning, organizing and documenting ancient coins found at the Agora site.
In 1961 Thompson published The New Style Silver Coinage of Athens for which she was awarded the American Numismatic Society's Archer M. Huntington Medal.
She was elected president of the Archaeological Institute of America (AIA) from 1964 to 1968 and vice-president to the International Numismatic Commission from 1973 to 1979.
In 1989, the Society created an endowment in her honor, the "Margaret Thompson Curatorship of Greek Coins."