Originally from Vermont, United States, Butler's parents were closely involved in the beginnings of the Seventh-day Adventist Church.
As a result of his rebuttals to the Marion party, which focused their dissent upon the ministry of Ellen G. White, Butler became one of the foremost apologists to defend her during the 1860s and 1870s.
Butler was active in raising funds to start Battle Creek College (now Andrews University), and to establish the Pacific Press in Oakland, California.
He started a vigorous evangelistic program, but when James White's health began to falter a second time, Butler was once again elected General Conference president.
By the time of the famous 1888 General Conference Session Butler called for those who were sympathetic to him to "stand by the old landmarks" or to not give up what he considered to be traditional theological positions.
The Butlers purchased a rural farm in Florida which they called "Twin Magnolias" and where they could raise citrus fruit and recuperate.