House was a pioneer and leading member of the Siam Mission of the Presbyterian Church U.S.A. He was born in Waterford, New York on 16 October 1817. He graduated from Union College, Schenectady, New York, with a bachelor's degree in 1837 and a master's in 1840. He received the M.D. degree from the College of Physicians and Surgeons, New York City in 1845. He was appointed to the Siam Mission in April 1845 along with the Rev. Stephen Mattoon and his wife to reopen the mission, although they did not finally arrive in Bangkok until March 1847. Although appointed as a physician, by 1852 he had abandoned medical work to undertake full time evangelism and, later, to engage in educational work as well. During his first furlough, 1855-1856, he married Harriet M. Pettit on 27 November 1855 and was ordained as a minister in January 1856. The Houses resigned left Siam in 1886 because Harriet's health was poor, and they resigned from the mission in 1887. She died in 1893, and Dr. House died on 13 August 1899. 

The most famous incident in House's life took place in 1868 on a trip to Chiang Mai. House was gored by an elephant, leaving him with a massive wound in his stomach. Although in shock, he had the presence of mind to sew himself up and send for help to Chiang Mai. Recovery required some six weeks, during which time he participated in the founding of the first church in northern Siam, the "First Presbyterian Church of Chiang Mai."