In an old-fashioned style jail-break, the pair cut through the bars of a window with a saw before scaling down the outer wall using a rope of knotted sheets, Ansa reported.
The men, both from Romania, then jumped over an external wall and fled by foot on Via Tiburtina.
At the time of their escape, they had been at a workshop in the prison's new annex, where there were just two guards on duty for 150 inmates, the prison guards' union, Sappe, told Ansa, adding that the alarm system wasn't working.
The men were named as 33-year-old Catalin Ciobanu, who was serving time for murder, and Mihai Florin Diaconescu, 28, who was in prison for burglary.
Prison escapes - and by using knotted sheets - are not such a rare occurrence in Italy.
In 2014, a prisoner in Sicily broke the bars of his cell at Pagliarelli prison and climbed down the wall on a rope of knotted sheets. The same man also managed to escape from a prison in Parma a year earlier.
In December 2013, two killers managed to escape a prison in northern Italy after being granted day release.