In his early career, he helped form and became the first president of the Cleveland Library Association in 1846 (later the Case Library). In 1850, he founded the short-lived Cleveland University. He also served as president of the Cleveland, Ashtabula, and Painesville Railroad, securing the financing allowing the line to complete its Chicago-to-Buffalo route. In 1846, Case was elected to Cleveland City Council and served as an alderman from 1847 to 1849. In 1850, Case was elected mayor of Cleveland. In his tenure, Case organized the city workhouse, poorhouse, and house of refuge. He is often credited with establishing the Cleveland nickname, "The Forest City", as a result of a city-wide fruit-tree planting campaign.