Philip Hammond has warned of a "rollercoaster ride" for the UK post-Brexit.
The Chancellor said the process - which will be triggered in March - would be "complex" over the coming two years.
But he said he was willing to take "whatever steps are necessary to protect this economy from turbulence".
The Conservatives will also abandon a plan to bring the country's finances into surplus by 2020.
But instead adopt a "pragmatic" approach following the vote to leave the EU, Mr Hammond said.
Speaking to the Conservative party conference in Birmingham, Mr Hammond said the policies of his predecessor George Osborne had been the right ones "for that time" - but times had changed.
"We will no longer target a surplus at the end of this parliament," he said. "But make no mistake, the task of fiscal consolidation must continue."
In his speech the chancellor added:
Guaranteed to continue payments of any multi-year grants secured by British businesses and organisations from the EU ahead of the UK's withdrawal.
Announced £220m of new funding for the tech sector to support efforts to transform biomedical and computer innovations into marketable products.
Said the UK corporation tax rate would fall to 17% by the the end of parliament.
Pledged continued support for the "northern powerhouse" project.
The Brexit vote dominated much of Mr Hammond's speech.
He said the message sent by voters on at during the referendum in June had been "received loud and clear".
"No ifs, no buts, no second referendum, we are leaving the European Union," he said.
Mr Hammond warned the decision to leave the EU had introduced "new fiscal uncertainty".
He also used his speech to poke fun at Jeremy Corbyn, joking the Labour leader had been a contender for the television show Strictly Come Dancing in place of Ed Balls, the former Labour shadow chancellor, until producers were warned he had "two left feet".
Ahead of his speech, Mr Hammond and Prime Minister Theresa May visited the construction site of a new HSBC office complex within sight of the Tory conference venue.
Neither wore hard hats or high-visibility jackets, the uniform favoured by George Osborne on similar tours, prompting some to draw parallels with the break from the former chancellor's polices.
Nonetheless, the chancellor's predecessor appeared to have no hard feelings, tweeting "good luck" to Mr Hammond ahead of his speech.