The carrier will offer 20 new routes from Frankfurt to "sexy" destinations across Europe in its winter 2017-18 flight plan, chief executive Michael O'Leary told a press conference at the airport.
Ryanair currently flies to Frankfurt-Hahn, situated about 120 kilometres from the city.
Summer 2017 will see the first-ever Ryanair flights depart from Frankfurt's main airport, after it struck a deal with operator Fraport - riling incumbent Lufthansa, which dominates traffic at Germany's largest hub.
In winter, the airline will boost its presence from two to seven aircraft stationed at the airport and add flights to capital cities like Rome, London and Madrid, as well as adding sun-soaked holiday destinations to those it offered in summer.
Ryanair hopes eventually to account for around 2.0 million of some 61 million passengers passing through Frankfurt each year, O'Leary said, with around 25 percent of those business travellers.
A boosted presence in Frankfurt extends Ryanair's challenge to Lufthansa, already angered by the airport's decision to charge the no-frills insurgent lower fees.
But Frankfurt will "never be a very large airport for Ryanair," the Ryanair chief said, in part because the Irish carrier is not interested in competing with Lufthansa and its low-cost subsidiary Eurowings for domestic German traffic.
Ryanair's presence at Frankfurt will peak at between 10 and 20 aircraft serving eight to 10 million passengers a year, he predicted.
O'Leary went on to offer a sober warning of the consequences of Brexit for the airline industry, a familiar theme for the rambunctious CEO.
Ministers in London "don't have an idea" what will happen once the UK quits common European air travel rules after leaving the EU in 2019, he said.
"You can't re-regulate this industry" without causing massive disruption, he added - suggesting that unless a deal is reached quickly, there could be "no flights to or from the UK in March 2019," when the two-year exit
negotiations are set to expire.
Britain is one of Ryanair's largest markets, accounting for around one-quarter of its revenues.
The airline has seen profits slide in the wake of the June vote to leave the EU, as the pound has slumped - meaning a smaller contribution from UK customers to the Irish firm's bottom line, denominated in euros.
"Things are going to change, and they're going to change for the worse" as Brexit approaches, O'Leary predicted, while expressing hope that "the English will change their minds" once the cost of quitting the EU becomes clear.