To celebrate the day of Manehattan's founding 400 years ago, Princess Celestia and Princess Luna organize the Pegasi Equestrian Express Race, a race where ponies and beings from all over Equestria and beyond come together to compete in the longest race in the land's history. It celebrates the pegasi who would traverse the then harsh landscape of the kingdom to deliver the mail between Vanhoover in the west, and Manehattan in the east, a route that inspired the modern railways. Everyone may compete, but not all will be victorious.

A young mailmare by the name of Derpy Hooves find herself participating in the race in order to save something she holds dear, but she has no idea what the adventure will bring.