The prime minister is expected to lay out a more concrete vision for Britain's immediate future relations with the EU by proposing a two or three year transitional deal broadly in line with our current membership terms.
She will also attempt to break the deadlock over the thorny issue of a Brexit bill by offering Brussels an £18 billion downpayment to cover budgetary obligations the UK has agreed to up to the end of 2020.
Ahead of the keynote address their was cautious optimism in Brussels, with EU officials are privately hopeful that Mrs May will deliver a realistic set of proposals that they can work with to reach the all-important "sufficient progress" threshold.
EU chief negotiator Michel Barnier and parliament rapporteur Guy Verhofstadt are both due to release statements immediately after the speech, in which it is understood they will not reject the PM's offer out of hand.
MEPs have already begun airing their views on what Mrs May is expected to say in her history defining address amid a sense of hope in European capitals that progress in the divorce talks may finally be looming into view.
German MEP Sven Giegold, who is finance spokesman for the Greens group in the EU Parliament, greeted her remarks with guarded optimism calling them a “step in the right direction”.
He said: “Theresa May takes the first step of facing reality. May's proposal for the transition period is a step in the right direction, but must not divert attention from the financial obligations that the UK has already made.
“Furthermore, a transition period comes with equal rights and equal obligations. There can be no special treatment for access to the internal market for Great Britain.
“May has to tell her citizens the plain truth. That means that her proposal must include the outstanding payments to Europe and should not give the impression that there is access to the internal market at special conditions.
“That includes paying the contributions to the EU budget, applying and enforcing all rules as well as the four fundamental freedoms including freedom of movement.
“This is the kind of truth and honesty British citizens never received from Brexiteers, but now could expect from their prime minister."
But Ukip MEP Jane Collins said Mrs May’s promise to make ongoing payments to the EU for a transition period amounted to a “bogus Brexit” that “betrayed” the 17.4 million people who voted leave.
She said: “Theresa May has now admitted that the Brexit the British people voted for will not be happening under her leadership. I have been warning about the bogus Brexit and it was a significant reason why I stood for the UKIP leadership.
"Now it should be evident to everyone that Ukip is needed and relevant to deliver the democratic will of 17.4 million people.
“The transitional arrangements mean that at the next general election the voters have a choice between someone who actually carries out there will or someone trying to call our bluff whilst delivering a Brexit betrayal.”