Originally allied with Carthage, Selinunte switched allegiance after the Carthaginian defeat by Gelon of Syracuse at Himera in 480 BC. Under Syracusan protection it grew in power and prestige. The city's growth resulted in a litany of territorial disputes with its northern neighbour, Segesta, which ended abruptly in 409 BC when the latter called for Carthaginian help. Selinunte's former ally happily obliged and arrived to take revenge.

Troops commanded by Hannibal utterly destroyed the city after a nine-day siege, leaving only those who had taken shelter in the temples as survivors; they were spared not out of a sense of humanity but because of the fear that they might set fire to the temples and prevent their looting. In a famous retort to the Agrigentan ambassadors who sought to negotiate for the survivors' lives, Hannibal replied that as they hadn't been able to defend their freedom, they deserved to be slaves. One year later, Hermocrates of Syracuse took over the city and initiated its recovery, though it soon fell back under Carthaginian control. Around 250 BC, with the Romans about to conquer the city, its citizens were relocated to Lilybaeum (Marsala), the Carthaginian capital in Sicily, but not before they destroyed as much as they could. What they left standing, mainly temples, was finished off by an earthquake in the Middle Ages.

The city was forgotten until the middle of the 16th century, when a Dominican monk identified its location. Excavations began in 1823, courtesy of two English archaeologists, William Harris and Samuel Angell, who uncovered the first metopes.