William McKendree was born in King William County, Virginia, on July 6, 1757. As a young man, he fought in the American Revolution against the British. Once the war was over, he became more and more interested in religious matters. He joined the Methodist Episcopal Church in 1787 and began to be work as a minister. He rode a circuit that spanned the states of Virginia, Maryland, North Carolina, and South Carolina.
In 1801, the conference sent McKendree to oversee the church's efforts in southeastern Ohio, Kentucky, Tennessee, and western Virginia. He served as a circuit preacher in addition to his organizational efforts, becoming a respected figure in the region. Because of his work, McKendree was elected as a bishop of the Methodist Episcopal Church in 1808, a position that he held the rest of his life. McKendree was the first Methodist bishop born in the United States. He earned the nickname "Father of Western Methodism" for his work.
In 1830, McKendree lent his support to the Lebanon Seminary, in Lebanon, Illinois. As a result, the school chose to change its name to McKendree College. The college still exists today.
McKendree's family had moved to Sumner County, Tennessee, in the meantime. When the bishop was not traveling, he also called the area home. He died at his brother's home in Tennessee on March 5, 1835.