Selectors began to take up allotments in 1862 and the townsite was established as Serpentine Creek in 1863. A Post Office under that name had been open since 1848, the name being changed to Serpentine in 1917.[2]
It eventually became the seat of the then Shire of East Loddon. Today, Serpentine is a producer of grain and cattle and a popular place for anglers.