A spokesperson at Frankfurt Airport reported that things were "very quiet" at the Lufthansa terminal. The kiosks were being staffed to rebook passengers and staff were handing out food and drinks to those who had to wait.
In Munich, nine out of 20 intercontinental Lufthansa flights were cancelled, while around 60 services at Hamburg Airport were grounded.
Cockpit called for a 35-hour strike on Monday at 1pm, cancelling 1,500 short- and medium-haul flights across the country. But that has extended to long-haul flight cancellations as well.
The strike will last until midnight on Tuesday.
It is the eighth strike called in an ongoing dispute between pilots and managements over pensions which has been going since April.
The key issue named by both sides is the airline wanting to raise the minimum retirement age from 55 to 60.
Jochen Rothenbacher, an analyst at Equinet Bank, said the most recent strike could cost the airline as much as €30 million.
Cockpit's strike started just hours after the Germany's rail service came back into action after a 50-hour strike held by the German Train Drivers' Union (GDL).
"When people can't get to work and goods can't be transported, the economy also suffers," said national transportation minister Alexander Dobrindt to Bild on Tuesday.
"Our transportation network is the central nervous system of our country. Comfort, growth and work places depend on it. This nerve system should not be allowed to go lame for long. A permanent blockade would massively hurt the economy."
Passengers stranded can rebook without charge or exchange their ticket for a train ticket.
More than 4,400 hotel rooms have been booked by the airline to accommodate stranded travellers.
Last week, pilots with Lufthansa's discount subsidiary, Germanwings, walked out for a 12-hour strike.