Mebane was founded when a post office was established in 1809. The new town was named for General Alexander Mebane of the North Carolina Militia. Alexander Mebane had also been a member of Congress from 1793 to 1795. In 1855, the railroad arrived. Mebane was incorporated in 1881, as Mebanesville. The name was officially changed to Mebane in 1883. The charter was amended to the City of Mebane in February of 1987.
The first public water supply and wastewater treatment facilities were constructed in 1921, and Lake Michael was completed in 1953.
Early government consisted of a Mayor and four Town Commissioners. Today, the main Municipal Building at 106 E. Washington Street houses the Water Department, the City Manager and Administrative offices, as well as the City Council Chambers.
In 1900 the census count was 218. An increase to 693 was noted in 1910. By 1920 this total had swelled to 1351, and in 1930 it was tallied at 1568. The official record in 1940 was 2060, and in 1950 the number of people was set at 2068. It should be noted that this figure is for the population dwelling inside the corporate limits of the town, and does not include those persons residing in the rural areas. The estimated population of Mebane in 2003 was 8,500.