Ignazio Marino is due to travel to Philadelphia this week, where the pontiff is scheduled to arrive on Saturday to take part in the Catholic Church's World Meeting of Families.
But the left-wing mayor has been criticized by his predecessor, Gianni Alemanno, who on Twitter accused Marino of running away from Rome.
“And Marino leaves again for the USA. With the excuse of accompanying the pope to Philadelphia he escapes once more from Rome,” said the right-wing politician.
Criticism also came in from other users of the social media site. One person said the mayor was “embarrassing, each day an excuse”, while others suggested he should not bother returning to Rome.
Marino said such controversy was needless and that the trip was intended to help his city.
Ancora inutili polemiche per un viaggio al servizio della città. Facciamo chiarezza http://t.co/ApJjrF1Gp0— Ignazio Marino (@ignaziomarino) September 22, 2015
“It's a matter of a very short but very important trip, in a historic moment for the Church and the US: it's the visit of Pope Bergoglio [Pope Francis' birth surname] in the US,” Marino told Il Messaggero.
The mayor promised his tour would prove financially beneficial for Rome, with a private meeting set up which could see an unnamed donor give up to €50 million to the city's archaeological sites.
Italian consulates in New York and Philadelphia have also organized events for the mayor to present projects financed through philanthropy. His trip to Philadelphia will be paid for by his hosts, Marino's office told Italian media.
Marino's jaunt stateside comes shortly after his summer trip to the US, during which the Italian government made a critical decision on the future of Marino's administration. Lawmakers in August voted against dissolving Rome city hall over the “Mafia Capitale” scandal which revealed widespread corruption that has cost the city millions of euros.
Gangmasters who for years siphoned off money from vital services such as rubbish collection and migrant centres are due to go on trial later this year. Alemanno was put under investigation in December, while Marino has faced calls for his resignation over the scandal despite not being part of the probe.