The airline said it had cancelled about 800 flights at its main bases in Frankfurt and Munich on Friday, affecting 130,000 passengers, and said it was working flat out to minimise the impact of the strike.
Labour union Vereinigung Cockpit (VC) had called on more than 5,000 Lufthansa pilots to stage a 24-hour walkout, saying the latest round of wage talks had failed.
Strikes and staff shortages have already forced several airlines, including Lufthansa, to cancel thousands of flights this summer, leading to long queues at major airports, frustrating people keen to start travelling again after COVID-19 lockdowns.
Passenger Liane Dickson was due to fly to Amsterdam from Johannesburg via Frankfurt, but the second leg of her flight was cancelled before she left South Africa.
"It is now 16 hours later and we have no email to say why it happened, what should we do next," she said at Frankfurt airport.
"At Johannesburg airport yesterday it was chaos because people didn't know whether they should check in their luggage to Amsterdam or to Frankfurt."
The VC union is demanding a 5.5% pay rise this year and automatic inflation compensation thereafter as well as better terms for entry-level pilots.
Lufthansa has said VC's demands would raise its staff costs by 40% or around 900 million euros ($899 million) over the next two years.
