The first believed interaction between colonists and the Esopus tribe was recorded in 1609. The Esopus tribe sold 72 acres of land to European colonists in 1652 through the Thomas Chambers land deed in Kingston, New York. It is unknown whether the two Esopus tribe sachems at the time, Kawachhikan and Sowappekat, understood the transaction, as in addition to a language barrier their culture had foundational differences in understanding money, ownership, and legal transactions. This deed began centuries of dispossession which continued through the Fisher/Rutgers Land Deed of 1899 and the Peter Stuyvesant Blockade.
The tribe fought a series of conflicts against settlers from the New Netherland colony from September 1659 to September 1663, known as the Esopus Wars, in and around Kingston. At the conclusion of the conflict, the tribe sold large tracts of land to French Huguenot refugees in New Paltz and other communities.
The Esopus Wars devastated many Lenape communities in what is now Ulster County. Populations dwindled through warfare with Dutch and French settlers, in addition to widespread disease, with smallpox being the most deadly. Casualties were exacerbated by inter-tribal warfare.