But, although likely to be a bumpy road, Monday's Brexit negotiations opened harmoniously, "on the right foot", as Michel Barnier the European Union chief negotiator put it, in the commission's headquarters in the Berlaymont - nearly a year to the day after the UK's dramatic vote to leave.
Amid reports that May is set to make a "generous offer" on the rights of European Union citizens remaining in Britain, the source saidLondon had been warned against doing so this week, on the grounds that it could drag up the thorny issue before talks had really got going.
May's government said in a statement it was "confident it can achieve a bold and ambitious deal that will work in the interest of the whole U.K".
"The most important thing I think now is for us to. think about the new partnership, the deep and special partnership that we want to build with our friends", said Johnson, who campaigned in last year's referendum to leave the EU.
After seven hours of talks in Brussels, Mr Davis - who had previously promised the "row of the summer" over the timetable for the negotiations - said he was optimistic about the talks.
"This first session was useful indeed to start off on the right foot as the clock was ticking", Barnier told a joint news conference with Davis at the end of the historic first session of negotiations in Brussels.
Despite positive promises of support on the matter May has has refused to unilaterally guarantee the residency rights of European Union nationals living in Britain, until reciprocal rights are in place.
Mr Davis also brushed off the idea Britain's negotiating stance could change given political instability in the UK.
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In contrast, Labour leader Jeremy Corbyn was pictured with those who have lost their homes and neighbours in Tuesday night's fire. On Wednesday, the apartment tower caught fire, the cause of which has not been established yet.
The meeting confirmed the EU's position that talks on the "future relationship", notably trade, would open only if "sufficient progress" was made in the priority issues, citizens rights, the financial settlement - the British Brexit bill, and the Irish Border.
The EU says it will not compromise on its core "four freedoms": free movement of goods, capital, services and workers.
Barnier said there will be one week of negotiations every month and the two sides will use the time in between to work out proposals. He said he views the talks with "informed optimism".
Anxious by immigration and loss of sovereignty, Britain previous year voted to end its decades-old membership of the 28-country bloc - the first state ever to do so - in a shock referendum result.
The vote came as a profound shock to Brussels against a backdrop of rising anti-EU sentiment, with many - including now US President Donald Trump - predicting the bloc's eventual break-up.
The government on Saturday said parliament would hold a special two-year session starting this week, sitting for double the normal time to allow it to overhaul European Union legislation.
British foreign minister Boris Johnson, like Davis a prominent backer of the leave campaign, also sounded an upbeat note.
While a member, the United Kingdom enjoyed free trade with the rest of bloc - a market that buys 44% of its exports and supplies 53% of its imports.