The action is the largest in a series of strikes over pay and conditions.
Ryanair staff pilots in Ireland, Germany, Sweden, the Netherlands, and Belgium were set to strike today for 24 hours, resulting in hundreds of the airline's flights being cancelled, including 20 to and from Ireland.
Last night, Ryanair said "it took every step to minimise disruption" to passengers.
Aircrafts of low-priced airliner Ryanair are parked at the tarmac of Weeze airport near the German-Dutch border during a wider European strike of Ryanair airline crews to protest slow progress in negotiating a collective labour agreement at Weeze airport, Germany, August 10, 2018.
Ingolf Schumacher, pay negotiator at Germany's Vereinigung Cockpit (VC) union, said pilots had to be prepared for "a very long battle" and that it could take months to push through change at Europe's largest low-priced carrier. But a court said yesterday Ryanair pilots in the Netherlands could not be prevented from doing so. "The strike may go ahead", judge Theo Roell said. Around 22 flights from Eindhoven airport could be hit.
Ryanair faced its worst one-day strike on Friday after a walk-out by pilots in five European countries disrupted the plans of an estimated 55,000 travellers with the budget airline at the height of the summer holiday season.
The airline has said that 85% of their flights will take off, "carrying nearly 400,000 customers across Europe".
Ryanair has refused to issue a list of the flights cancelled, but The Times understands that at least 50 departures from the United Kingdom have been called off, with more than 250 cancelled in Ireland.
The unprecedented simultaneous strike action is the latest headache in a turbulent summer for Europe's second-largest airline.
Ryanair, which averted widespread strikes before Christmas by agreeing to recognise unions for the first time in its 30-year history, has been unable to quell rising protests since over slow progress in negotiating collective labour agreements.
Since then, however, it has struggled to reach agreements.
But Ryanair pilots say they earn less than counterparts at other airlines like Lufthansa.
Another key complaint of workers based in countries other than Ireland is the fact that Ryanair employs them under Irish legislation, arguing most of its employees work on board Irish planes.
Ryanair's management claims to have offered a pay increase and to be open to further talks.
At a Frankfurt press conference on Wednesday, Ryanair's chief marketing officer Kenny Jacobs said the company's German pilots enjoy "excellent working conditions".
But chief executive Michael O'Leary has also warned the airline may shift jobs and planes to more profitable areas if the turmoil continues. But it has also threatened to move part of its fleet to Poland, which could mean a loss of jobs.