The two-story, L-shaped, Waioli Mission House has been a house museum since 1952. Its gable roof, white clapboard walls, multi-pane windows, and first- and second-story lanai well reflect the dwelling's time, place, and situation, by adapting New England forms to a tropical location. The present form is the result of several building episodes. Originally the kitchen, with its wraparound lanai, was a separate structure; however, in 1840, a dining room and pantry were added to connect this space with the main house. Twenty years later, a second floor bedroom was constructed above the dining room and pantry.
In response to the need for a missionary on the windward side of Kauai, William Alexander, his wife, and infant son, members of the fifth company of missionaries to come to Hawaii, were assigned to the Hanalei district in 1834. Within eighteen months of their arrival, Alexander reported that the thatched house, built by the Hawaiian community for the family, “leaks rotting the floor mats.” During the first half of 1836, Hawaiians gathered timber from the mountains which would be used to frame a new, Western-style house. Sandstone for the building's foundation was quarried from the mouth of the Waipa stream by the Hawaiians. With the aid of two American carpenters and several Hawaiians, the frame was raised in November 1836, and within a month, the roof of zinc sheets was in place. By April 1837, the original house was completed. Due to health concerns resulting from the damp windward climate, the Alexanders subsequently relocated to Lahainaluna on Maui. In 1846, the Reverend Abner Wilcox assumed the pastorate at Waioli Mission and occupied the house with his wife, Lucy, and their seven sons. Following the deaths of Abner and Lucy Wilcox in 1869, the dwelling fell vacant and remained so until 1921, when three of the Wilcox granddaughters undertook the restoration of the house, as well as the adjacent mission hall, using the architectural skills of Hart Wood. The restored residence remained in the Wilcox family's hands until 1952 when the house was deeded over as a house museum to a family-operated corporation.