Alexandria was platted in 1872 as the easternmost of a string of towns laid out alphabetically along the St. Joseph and Denver Railroad by the Nebraska Land and Town Company, and named for S. J. Alexander, a local figure who helped route the railroad and later served as Nebraska's Secretary of State. The town absorbed residents from the now-vanished nearby settlement of Meridian and weathered several severe 1870s-80s storms, including a school-destroying 1875 tornado.

Alexandria's population has more than halved since 2000 (from 216 to 146 in 2020), a common pattern for the county's smaller villages, but it retains local pride through achievements like its 1996 Class D state softball championship and its connection to Wyoming governor Bryant B. Brooks.