British Prime Minister Theresa May, who backs the scheme, was in the Commons as MPs voted 415 to 119 to support a third runway at Heathrow.
As the marathon debate continued, the central lobby in the Houses of Parliament was placed into a security lock down for a while after 12 anti-Heathrow expansion demonstrators staged a "lie-in" on the floor. They chanted and sang songs, before peacefully leaving the area.
Police in London said the protest had been dealt with by security staff and there were no arrests.
Transport Secretary Chris Grayling described the 19-billion US dollar Heathrow expansion as Britain's biggest transport decision in a generation.
He said the planned third runway will be built at no cost to taxpayers, with the expansion scheme funded by the private sector. Grayling said it will create a massive economic boost to Britain, with new international routes, more than 100,000 new jobs, doubled freight capacity and benefits worth around 100 billion dollars to passengers and the wider economy.
Grayling said: "This is a momentous vote that has been 50 years in the making and represents the biggest transport decision in a generation. Successive governments have wrestled with the issue of Heathrow expansion but never before has parliament held a vote on this project. At stake are thousands of new jobs and the country's ability to compete on an international stage and win new global trade."
He told MPs during the debate the project is in the strategic will put Britain in a good position in the post-Brexit world. He said the project has been delayed too long already and must be put on track.
Labour's shadow chancellor John McDonnell, whose parliamentary constituency will be hit by the expansion, said some villages 1,000 years old will be wiped off the face of the earth if the Heathrow plan goes ahead, adding "my constituents find it heartbreaking".
McDonnell said the environmental impact of a bigger Heathrow posed a threat to the planet, adding the project should be blocked "because it's so dangerous for climate change."
He said a totemic European-wide campaign will be waged to fight the Heathrow expansion plan.
The vote followed a government decision on June 5 to officially support the expansion of Heathrow through a third runway, put forward in a proposed Airports National Policy Statement (NPS).
If the scheme goes ahead it will see the construction of the first full-length runway in the southeast of England since the Second World War.
A 3.5-billion dollar package will contribute towards the cost of compensation and mitigation measures for people affected by the expansion, as well as noise insulation and community amenities. There will also be a 6.5 hour scheduled night flight ban and noise restrictions which will be legally enforceable.
Although MPs voted by a majority to back the Heathrow project, it will still have to make its way through Britain's planning procedures, though government and parliament backing is seen as crucial steps.
Last week, government cabinet minister Greg Hands resigned, saying he wanted to fulfill a pledge he made to his constituents to oppose the Heathrow plan.