Alsium was destroyed in the 6th century AD, during the Gothic War, by the Ostrogoths led by Totila. Later a castle, named Palo, was built in the area: it was a fief of the Orsini and, from 1693, of the Odescalchi family.
Modern Ladispoli was founded in 1888 by Ladislao Odescalchi, whom its name stems from.
In the late 1970s and until the early 1990s, parts of Ladispoli served as refugee camps for Soviet emigrants seeking political and/or religious asylum in Western countries (mostly United States, Canada and Australia). The experience of Jews from the former USSR staying in Ladispoli in the 1980s was first described in English by Maxim D. Shrayer in his literary memoir "Waiting for America" (2007).