Ministers will decide on Tuesday whether to give the go-ahead to a new runway at Heathrow despite internal opposition from senior Tories including Boris Johnson and Justine Greening.
Mr Grayling insisted that no verdict had yet been reached on which of the three options for expansion at Heathrow or Gatwick would be backed by the Government.
He acknowledged that any of the three options on the table - new runways at Heathrow or Gatwick, or extending an existing runway at Heathrow - would be controversial but they would “open up new opportunities for Britain” as it adjusts to Brexit.
His comments came as the Sunday Telegraph reported that Tory MPs were prepared to support a legal challenge by Conservative councils if Mrs May decided to press ahead with a third runway at Heathrow.
The newspaper reported that rebel MPs will advise a legal challenge from Tory authorities to ensure expansion is “killed off” in the courts.
The Sunday Telegraph also highlighted newsletters from Mrs May to her constituents in Maidenhead pledging to “fight to stop the third runway” at Heathrow, warning it would have a “detrimental” impact on their lives.
Tory policy at the time of the leaflets in 2009 and 2010 was to oppose the construction of a third runway.
A 2009 newsletter said: “Theresa has opposed the Government’s decision to approve a third runway at Heathrow. This would have a major impact on the constituency. A particular concern is a possible earlier increase in night flights over Maidenhead and the surrounding area.”
Mrs May is quoted as saying a third runway would be a “major blow to local residents”.
After the coalition took office in 2010, a leaflet in November that year welcomed the news that the third runway project had been cancelled.
Meanwhile, the Sunday Times reported that the Cabinet sub-committee making the decision on Tuesday would be presented with plans to offer residents near Heathrow a “world-class” compensation package.
Those living in around 4,500 homes that will either be demolished or could suffer blight because they are so close to the airport will be offered the market value of their houses plus 25% as well as all legal fees and stamp duty costs paid, according to a leaked report drawn up by the business analysts Ernst &Young.
Mr Grayling said all three options for expansion were still in play: “Genuinely it’s going to be a decision on Tuesday and it’s a difficult one, because all three of these are well-crafted proposals and any one of them could bring benefits to the UK.”
Mrs May has moved to head off possible Cabinet resignations by giving ministers freedom to speak out against the Government’s decision, with the possibility of Heathrow expansion fiercely opposed by Foreign Secretary Mr Johnson and Education Secretary Ms Greening.
“There will be challenge and opposition, whatever option we take,” Mr Grayling told BBC One’s Andrew Marr Show.
“The question here is that we have to, in my view, take a decision that is in the interest of our nation.
“What delivers us the best connectivity, the right approach for the future at a time when we want to grow international trade links, open up new opportunities for Britain.
“Of course there will be opposition, of course there will be challenge whatever we do.”
Supporters of Heathrow have argued that a single hub airport is vital for connecting the UK to the world, but Mr Grayling indicated that new passenger jets made that less vital than in previous years “so there are genuinely competing arguments here”.