He worked as a bank clerk in New York, New York. He suffered poor health, spending much time in the western states of America. In 1885 he entered Harvard Law School, graduating in 1888. Wister practiced law in his home town Pennsylvania before devoting himself to writing. In 1898 he married Mary Channing, his cousin, and had six children.
His Wild West writing is what made him famous. A friend of Theodore Roosevelt, he often hung out in Wyoming (then still fairly wild; the Johnson County War took place in 1892) to get away from Eastern life.