Ben-Hur: A Tale of the Christ – 50 million
Lew Wallace wrote this biblical tale, publishing it in 1880. It cleverly discusses the life and times of Jesus Christ indirectly, using the protagonist, Judah Ben-Hur, to observe Christ and other aspects of life in that era. Wallace meticulously researched the historical accuracy of the novel. It is credited with popularizing novels in the U.S., since the religious themes made it more palatable to readers at the time.
The sales number is an estimate – it was enormously popular in the years after it was first published, but few people read the novel these days. It's more likely you've heard of it because of the 1959 film starring Charlton Heston.