A year after Britain's seismic referendum, Brexit minister David Davis and the European Union's French chief negotiator Michel Barnier will meet at the European Commission in Brussels at around 0900 GMT.
At stake in hugely complex talks facing a March 2019 deadline is not just Britain's future but a western political order that would be badly shaken by a failure to reach a deal.
The situation is very different from 12 months ago when the Brexiteers were riding high, with Prime Minister Theresa May's entire approach called into question after a disastrous election performance on June 8.
"While there is a long road ahead, our destination is clear -- a deep and special partnership between the UK and the EU. A deal like no other in history," Davis said in a statement as he headed into the talks.
"I look forward to beginning work on that new future."
British foreign minister Boris Johnson, like Davis a prominent backer of the leave campaign, also sounded an upbeat note.