The expansion comes a day before the deadline for a crucial capital injection into struggling Italian flag carrier Alitalia which has been on the brink of having its planes grounded, but Ryanair said its move should help the airline in its efforts to restructure.
Ryanair announced it will base six aircraft at Fiumicino, Rome's mostly domestic airport, and slowly transfer the flights it had operated from Ciampino airport and increase to nine the number of domestic Italian routes it flies.
The number of aircraft based there could double within a year as it receives new aircraft from Boeing.
Ryanair said it would continue to develop domestic and international flights from Ciampino, the mostly international airport.
Ryanair said its one-way flights on new domestic routes will start at €49 including taxes, compared to €75 on Alitalia flights.
Nevertheless Ryanair said this would benefit Alitalia as it would ensure the feeding of passengers into the international flights it operates from Fiumicino.
"Ryanair will guarantee that connectivity to Rome and to southern Italy will be maintained regardless of Alitalia's plans to reduce capacity on domestic routes," said Ryanair's deputy chief executive Michael Crawley in a statement.
The Irish airline said it was willing to cooperate with Alitalia, an offer the Italian company swiftly rejected.
"Alitalia thanks Ryanair for its proposal to collaborate at Rome Fiumicino airport, but we have our own strategy..." said the Italian airline.
A €300 million Alitalia capital subscription expires on Wednesday.
Air France-KLM, which owns a 25 percent stake in Alitalia, has said it won't participate as it believes the restructuring plan put forward by the company won't lower costs sufficiently to make the airline successful.
The Italian government is looking for another major international airline to partner with Alitalia.
The state-owned Italian postal service has been tapped to contribute up to €75 million in the capital increase, triggering rivals' allegations of illegal protectionism.
Alitalia says Italian banks are also lined up to lend it €200 million.
The airline was already bailed out by taxpayers five years ago in a controversial operation that handed a consortium of private Italian companies a majority stake, part of which was later sold to Air France-KLM.
But it still struggled and racked up losses, with its debt now standing at €1.2 billion.
It was nearly grounded last month when Italian energy group ENI threatened to stop fuel supplies because of unpaid debts.