The walkout - the 14th since April 2014 - has affected more than 315,000 passengers, with the airline forced to cancel 2,618 flights over three days.
The Lufthansa pilots going on strike are demanding a pay rise of an average of 3.66 per cent per year, retroactive for the past five years.
Their union says pilots have endured a wage freeze over that time and suffered a "significant loss of purchasing power" due to inflation, while Lufthansa has made billions in profits.
Lufthansa's hub management board member Harry Hohmeister said it was "not possible" to meet the pilots' demand for a bigger wage hike.
"The starting point is that we already pay our pilots far better than our competitors," he said.
Affected passengers can rebook their flights without charge, the airline said.
It has also booked thousands of hotel rooms for stranded travellers, while camp beds have been set up at Frankfurt airport for passengers who do not have a valid visa to enter Germany.
Bild daily said the strike costs the airline some 10 million euros (USD 10.5 million) a day.
In July, it brought an end to the long-running industrial dispute with cabin crew through a deal on pay and working conditions, including a no-strike agreement and job guarantees until 2021.
Lufthansa group's other airlines - Germanwings, Swiss, Austrian Airlines, Air Dolomiti and Brussels Airlines - are not affected by this week's strike.
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