British Airways said it would fly more than 60% of passengers with flights booked for this weekend despite a three-day cabin crew strike that risks hurting the labour government weeks before an election.
The walkout over pay and jobs will disrupt travel for thousands after talks between the Unite union and management collapsed.
A BA flight to Tel Aviv late on Friday was the last to leave London's Heathrow before the action formally started at midnight. A further four-day strike is planned later this month.
Prime minister Gordon Brown called for both sides to resolve their differences without delay, as political opponents sought to capitalise from Unite's position as his party's biggest single financial backer.
The prospect of the first national rail strike for 16 years added to the government's problems after signal workers voted for industrial action on Friday, although peace talks were due to be held next week.
Labour has strong union ties that go back to its foundation in 1900. The political director of Unite, Britain's largest union, is Brown's former spokesman.
The opposition Conservatives, favourites to win an election expected on May 6, called on Brown to sever financial links with the union during the dispute.
"Labour's dependence on funding from Unite is compromising their ability to stand up to the unions and stand up for the interests of passengers," Conservative transport spokeswoman Theresa Villiers said.
BA, which has 12,000 cabin crew, wants to save an annual £62.5 million ($95 million) to help cope with a fall in demand, volatile fuel prices and increased competition from low-cost carriers.
BA chief executive Willie Walsh apologised for the disruption to passengers in a video on the carrier's website.
He said the airline was well prepared and would put contingency plans into operation.
"We are going to fly as many of our customers as possible. We are going to fly you safely in secure conditions and we are going to fly you in comfort," Walsh said.
Tony Woodley, Unite's joint general secretary, accused Walsh of declaring war on the union.
The airline has retrained 1,000 staff to stand in as temporary cabin crew, found passengers flights on rival airlines and chartered aircraft and crew to fulfil other routes.
Many crews, including those working on long haul flights from London Gatwick airport and all flights from the smaller London City airport, will not take part in the action as they have already agreed to proposed changes.
The airline normally transports 70,000 passengers daily, and hopes to fly 49,000 a day during the weekend strike.
