Their existence was first noted by Europeans in April 1564 when a French Huguenot expedition under Rene Goulaine de Laudonniere went up the St. Johns to the mouth of the Ocklawaha and found several fortified villages. They were protected by palm trunk walls and united by roads cut thru the surrounding forrests. The people themselves were described as "splendid physical specimens" who had well-tended fields and abundant fish and game. Their religion appeared to be based on the stars and the moon, and recognized the sun as the primary deity. Each spring, the Acuera held a special ceremony honoring this supreme god and made offerings to it.
In 1566, Spain sent Pedro Menendez de Aviles to eradicate the French toehold in Florida. This included an expedition up the St. Johns, where his men also noted the Acuera villages. But, the tribe was hostile to them, intent upon preventing them for going further upriver than the narrows at Lake George near modern Astor. Not only did they place log barriers in the water, they also launched an archery strike that forced the expedition to return to St. Augustine.
Spanish priests were more successful in penetrating the Acuera homeland, establishing Roman Catholic missions amongst them by 1616. These included the missions of San Luis and Santa Lucia, where the natives were encouraged to give up mere subsistence in favor of full-time farming. Unfortunately, these priests also brought new diseases to the remote tribe, decimating their numbers until they were forced to abandon the missions altogether by 1675.