The University neighborhood includes both the University Circle and Little Italy areas. It became part of the City of Cleveland when portions of East Cleveland Village and East Cleveland Township were annexed to the City in 1872 and 1892 respectively.

University Circle experienced its first development in 1799 when Nathaniel Doan established a tavern and hotel at the present intersection of East 107th and Euclid. "Doan's Corners" grew rapidly as a stopping point for travelers between Cleveland and Buffalo.

The area's modern history began in the 1880's with the donation of 63 acres of wooded parkland to the city by industrialist Jeptha Wade and the relocation to the area of Western Reserve College and the Case School of Applied Science. Other major institutions soon followed, including the Art Museum, the Museum of Natural History, Severance Hall and University Hospitals. Just north of the institutions, land along Wade Park Avenue and Magnolia Drive became the site of numerous stately residences, many of which were occupied by trustees of the institutions.

Today, University Circle -- with sixty cultural, educational, medical and religious institutions clustered in a 488-acre campus setting -- is unique in the world with respect to the number and diversity of its institutions.

Little Italy is a compact neighborhood focused along Mayfield Road and tightly bounded by the hills of Lakeview Cemetery on the east and north, the former Nickel Plate Railroad on the west and Case Western Reserve University on the south. In the late 19th century, Italian immigrants were drawn to the area principally by opportunities for employment as stone cutters at the Lakeview Marble Works.

The area north of Mayfield Road was densely developed with modest wood-frame houses by 1895. The area south of Mayfield was developed principally between 1905 and 1915. The four-day annual celebration, the Feast of Assumption, sponsored by the Holy Rosary Church, attracts crowds of up to 100,000 in a single night.