Lufthansa has cancelled 1,300 flights after it lost a last-minute legal bid to halt a strike by cabin crew.
The two-day action over pay and conditions began at midnight local time. About 180,000 passengers are set to face travel disruption.
The UFO union said it would hit all Lufthansa flights from German airports.
Flights by Lufthansa's other airlines including Eurowings, Swiss, Austrian Airlines, and Brussels Airlines are not affected, the airline said.
Lufthansa has cancelled 700 flights on Thursday and 600 on Friday, amounting to about one-fifth of its planned flights over the 48-hour period.
It said it regretted the inconvenience caused, adding: "We will do everything we can to minimise the impact of this massive strike on our customers."
On Wednesday, a Frankfurt labour court rejected Lufthansa's application to prevent the strike, which is part of a long-running dispute at the airline.
Lufthansa has said passengers travelling between German airports can exchange their tickets online for rail tickets. Other passengers will be offered alternative flights.
The union's vice-president, Daniel Flohr, has warned that further strikes could come "at any time".