Eastern High School was founded in 1844 as an all-female high school in Baltimore, Maryland. The city had decided to start two such high schools for women: Eastern and Western, which would serve their respective side of the city. These schools were designed allow female students to continue their grammar school education and took students as young as twelve years old if they could pass the entrance exam.

When the school opened, it was located at 101 North Front Street, but quickly outgrew the building. The school was then moved to 301 Aisquith Street (now 249 Aisquith Street). The original building was demolished and a larger, Italian Villa style building, designed by Colonel R. Snowden Andrews took its place. The students took up residence in a private home on Baltimore Street during the construction period. The new school opened in 1870 and remained in use until 1906, when once again the school population outgrew its building. The curriculum also continued to develop and expand to cover subjects that were requirements in the male curriculum. Students also began to participate in extracurricular activities and clubs. The school moved for a third time to 1701-1735 North Avenue and reflected the changing requirements for female education. A gymnasium, laboratories, and a large auditorium were added.

In 1938, the school moved once again to 33rd Street into an even grander building in the Waverly neighborhood. The new building had all of the modern educational accoutrements, including typewriting rooms, and was wired to with a broadcast system throughout the entire school. The school population had expanded to over 2,000 students. The school fell into decline during the seventies and eighties and low enrollment forced a switch to co-education in 1984. A magnet business curriculum was also added to boost interest in the school. Eastern High School eventually closed in 1986 because of falling enrollment, as necessary renovations to the building had become too costly. Johns Hopkins Medicine purchased and fixed up the building in the 1990s; it now serves as office space.