Edinger began her professional career in 1921 as a paleontology research assistant at the University of Frankfurt, a position she held until 1927.

[6] She was heavily influenced in her work by Otto Schindewolf, Louis Dollo and Friedrich von Huene, contemporary vertebrate paleontologists.

[2] For the next five years, she continued to work in secret at the Naturmuseum Senckenberg under the protection of the Museum Director, Rudolf Richter.

In December 1938, Phillipp Schwartz former professor at the University of Frankfurt, used his formerly established Notgemeinschaft Deutscher Wissenschaftler im Ausland society to provide aid to Edinger.

[2] On May 11, 1940, she arrived in New York and soon after moved to Massachusetts to take a position at the Harvard Museum of Comparative Zoology, where she published her second seminal work, The Evolution of the Horse Brain in 1948, three years after becoming a citizen of the U.S.[1][5] She took leave from Harvard for the 1944–1945 academic year to be a professor of comparative anatomy at Wellesley College, a position she resigned after her hearing deteriorated severely.

[6][3] Edinger's work on fossil horse brains showed that evolution was a branching process, as structures could evolve independently, such as the large forebrain found in advanced mammals.

[6] During her time in Cambridge, Edinger would often return to Frankfurt to visit, as she was very loyal to her hometown for presenting her with an honorary degree.

Her early education was provided by several governesses, many of whom taught in both French and English - a quality that proved to serve her well later in life.

[5] Her study of the brain of Nothosaurus, a Triassic marine reptile, earned her a Ph.D. in natural philosophy in 1921 and was the topic of her first publication.

Her significance in the pre-existing topic of endocasts was that she observed the relationship between the brain/braincase and different vertebrate classes rather dismissing the notion that the braincase was of no reliable use.

[2] Her father, Ludwig Edinger, identified ancient and modern areas of the vertebrate brain and she built on his ideas by introducing the concept of time brought by stratigraphic occurrence.

She brought forth the notion that ancient anatomy was not present in living vertebrate, thus calling for the determination of the sequence of innovation with the use of fossils.

Her neonatological[15] comparisons were challenged by George Gaylord Simpson and because of this, she suggested a strong analysis of brain enlargement and patterns of cortical sulcation and how they arise independently.

She also noted that neural and osteological innovations in horses did not happen at the same time or rate as other body systems, further arguing her point.

Since she was highly experienced in the field of neuroanatomy, Edinger was able to withdraw additional information from endocasts, such as neural input.

[2] Another notable contribution to Edinger's scientific legacy was in her strong critiques of Othniel Charles Marsh's interpretations of the “General Laws of Brain Growth”.