The two-day strike over pay began at midnight local time, with Lufthansa saying about 100,000 passengers will be affected.
Flights by Lufthansa’s other airlines including Eurowings, Swiss, Austrian Airlines, and Brussels Airlines are not affected, the company said.
The industrial action is part of a long-running pay dispute at Lufthansa.
The pilots’ union, Vereinigung Cockpit, has organized 14 strikes since April 2014.
On November 22, Lufthansa made two legal challenges to halt the strike.
A Frankfurt labor court first rejected Lufthansa’s application for an injunction. Later in the evening, the Hesse state labor court rejected the airline’s appeal.
Pay talks between the Vereinigung union and Lufthansa broke down earlier this month, and Lufthansa said the union had “consistently rejected the offer” of mediation.
The Vereinigung is calling for a 3.7% pay rise for 5,400 pilots dating back to 2012.
Lufthansa, which is facing increasing competition from budget rivals, offered a 2.5% increase over the six years until 2019.
Meanwhile, a separate dispute with cabin crew at Lufthansa’s low-cost subsidiary, Eurowings, led it to cancel more than 60 flights on November 22.
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