E. Margaret Burbidge began her research career at Yerkes Observatory in 1951, having been encouraged by O. Struve and S. Chandrasekhar to accept a research fellowship from the International Astronomical Union. She thrived in this new environment which fostered making connections between physics and astronomy. She was inspired by a pivotal conference at Yerkes in 1952 organized by Maria Mayer and Harold Urey on the abundance of the elements at the time she was analyzing spectra of B stars using spectrographs at Yerkes and at McDonald Observatory. Subsequently she pursued abundance anomalies in stars and began to work on chemical evolution in galaxies and on the origin of the elements. After her ground-breaking paper on stellar nucleosynthesis with Geoffrey Burbidge, William Fowler, and Fred Hoyle, in 1957 she returned to The University of Chicago as a Shirley Farr Fellow and measured galaxy rotation curves at McDonald Observatory. In 1962 she accepted a professorship at the University of California at San Diego where she spent the rest of her career (except for 1972 - 1973 when she was Director of the Royal Greenwich Observatory). She was elected president of the American Astronomical Society 1976 - 1978 and president for the American Association for the Advancement of Science in 1983. In 1985 she was awarded the National Medal of Science.

Margaret Burbidge's research concerned the chemical evolution of galaxies and she synthesized a number of astrophysical fields: nucleosynthesis in the cores of stars; abundance patterns in both stars and the ionized interstellar medium; mixing of gas in both quiet and violent galactic environments; the physical connection between small scales (nuclei and star-forming regions) and large scales in galaxies; and the relationship between galaxies and their environment. As one path to understanding the connection between stellar populations and the structures of their host galaxies, she measured dynamical masses and mass-to-light ratios for a wide range of galaxy types. High-velocity gas in some sources suggested out-of-equilibrium conditions, a line of research that put her at the forefront of interpreting the emission and absorption spectra of quasi-stellar objects immediately after their recognition in 1963.