Elizabeth "Lizzy" Myers and her parents, from Lexington, Ohio, were given special seats at Francis's general audience in St. Peter's Square, where the pope spoke to them briefly.
He bent down so his head could reach the level of Lizzy's, softly touched the girl's eyes with his right hand and blessed her.
"She was awestruck. She just teared up," her mother Christine Myers, who is Catholic, told reporters afterwards. "To her he's the big guy in the white hat."
"He asked us to pray for him and told us he would pray for us," she said. "I feel an absolute sense of peace. For the first time, I've felt peace."
Lizzy, whose case has received big media coverage in the United States, is not aware that she is suffering from Usher's Syndrome, which will eventually leave her deaf and blind.
Her parents said they would tell Lizzy, who already wears a hearing aid, about her condition gradually as she asks questions.
She could be blind in about seven years so they have started what they call a "visual bucket list" of sites and people they think she should see while she can.
Seeing the pope was among the experiences at the top of the list. She also saw the Colosseum and other monuments in Rome.
"I feel like I have very little time to show her so much," her father, Steve Myers, said.
After reading of her case, an airline offered them round-trip tickets to anywhere in the world and the family chose Rome.
Lizzy gave the pope a piece of a meteorite she was given when she was a special guest at the Warren Rupp Observatory in Mansfield, Ohio, one of the first places on her parents' list.
Her mother said she and her husband wanted to make sure that she also saw simple things while she could, "like bonfires and fireflies".