Complete with Vatican logos on headrests and air hostesses' uniforms, the inaugural flight traveled from Rome's Fiumicino airport for the shrine of Lourdes in France.
The charter flight's slogan spoke volumes about what its clients are doing above the clouds: "I'm Searching for Your Face, Lord."
"It is a spiritual journey," explained Francesco Gherra, one of the pilgrims who boarded Monday's inaugural flight hosted by Cardinal Camillo Ruini, the former head of Italy's bishops.
The Vatican aims to serve 150,000 pilgrims a year on its chartered Boeing 737, run by Italy's Mistral Air.
Destinations range from the shrine of Fatima in Portugal to Mount Sinai in Egypt, where Moses is said to have received the 10 Commandments from God.
In-flight entertainment on the way to the world's holy sites will, somewhat predictably, be religious in nature, the Vatican said.
"The crew has been informed that there are (religious) messages that will be transmitted, that films will be shown during the flight," said Father Cesar Atuire at the Vatican office coordinating pilgrimages.
Keeping costs for pilgrims low is another Vatican priority, Atuire said.
The Vatican's venture into the airline industry did not go unnoticed by competitors, including Ryanair, Europe's biggest low-cost carrier.
The Vatican hopes to fly pilgrims from Rome to Santiago de Compostela in Spain, a route already serviced by the low-budget carrier.
"Ryanair already performs miracles that even the Pope's boss can't rival, by delivering pilgrims to Santiago de Compostela for the heavenly price of 10 euros," Ryanair said in a statement.