Although Christianity still exists in post-War America, its overall influence has waned. Many new religions have sprung up in its place. Where Christianity still holds sway, it has scattered into even more splinter groups, such as the Catholicism-derived Saint Monica's Church in Rivet City and the Abbey of the Road, a Christian monastery somewhere west of the Commonwealth. Mormonism still exists as well, predominately in the town of New Canaan.
- James and his wife were particularly fond of a passage, specifically Revelation 21:6 from the Christian New Testament: "I am alpha and omega, the beginning and the end, I will give unto him that is athirst of the fountain of the water of life freely." They later used this as an inspiration for Project Purity.
- John Cassidy has at least some knowledge of Christianity, noting that the "good book" does not mention the possibility of the Garden of Eden coming in a kit.
- Marcella is a Christian missionary located at Point Lookout.
- Father Clifford and his acolyte Diego of St. Monica's church are notably Christian.
- O'Hanrahan, a Private in the New California Republic Army, was raised a Christian.
- Father Donald, a Christian priest of Cold Water.
- Daniel, a Mormon missionary from the New Canaanites, who leads and teaches the Sorrows in Zion Canyon.
- Joshua Graham, also a Mormon missionary from the New Canaanites, who was one of the founders of Caesar's Legion. After losing the First Battle of Hoover Dam however, he was lit on fire and thrown into the Grand Canyon. He survived and this experience caused him to be reconverted to Mormonism. He leads the Dead Horses in Honest Hearts.
- The Yangtze Memorial's cross predated the bombs, and is not an indication of any current Christian influence.
- Dialogue choices throughout Honest Hearts heavily imply that the Courier has never heard of Christianity.
- The Courier may obtain a copy of Scripture, the holy book of Christianity, after completing Honest Hearts.