The marathon will feature more than 1,200 people reading the Old and New Testament in over seven days and six nights.
While the pope recited his segment from the Vatican, most of the reading will be done live in Rome's Santa Croce in Gerusalemme, a basilica built in the fourth century.
Besides Roman Catholics, members of other religions, including Jews, Protestants and Orthodox Christians will participate.
Benedict, who appeared on a giant screen mounted in the church to start the marathon, was followed by Bishop Ilarion, a representative of the Russian Orthodox Church. Oscar-winning director Roberto Benigni was also among those reading from the Bible on Sunday.
Outside the packed basilica a crowd gathered in front of the torch-lit facade.
Every few chapters the reading was being interrupted for Christian or Jewish religious music, and opera star Andrea Bocelli led the first interlude Sunday by singing Bach's "Praise the Lord."
"The word of God will enter the homes and accompany the lives of families and individual people," Benedict said of the program following his traditional noontime blessing on Sunday. "If welcomed, this seed will not fail to bring abundant fruits."
Addressing faithful gathered in St. Peter's Square, Benedict noted the televised marathon would run parallel to a worldwide meeting of bishops on the relevance of the Bible for contemporary Catholics. The meeting of 253 bishops, known as a synod of bishops, will run from Monday through Oct. 26.
The Bible marathon is scheduled to end with Cardinal Tarcisio Bertone, the Vatican's No. 2 official, reading the last chapter of the Apocalypse.