Legislation for Phase 2a of HS2 has passed its final hurdle.
The parliamentary Bill to build the high-speed rail line between Birmingham and Crewe received royal assent on Thursday, opening the way for construction work to begin.
Prime Minister Boris Johnson described it as a "landmark moment".
Construction of Phase 2a is expected to begin by 2024.
The opening of the route will coincide with Phase 1 between London and Birmingham, which is scheduled to happen between 2029 and 2033.
This means the first HS2 trains will run on new high-speed lines between London and Crewe via Birmingham, before joining the existing network to create direct services to locations such as Liverpool, Manchester, Preston, Carlisle and Glasgow.
HS2 continues to face strong opposition.
Some environmental groups are angry at the impact of its construction, with a number of campaigners in tunnels dug near London Euston station.
There are also widespread concerns about the cost of the project
The Government-commissioned Oakervee Review warned in 2018 that the final bill for HS2 could reach £106 billion at 2019 prices.
Mr Johnson said: "Today is a landmark moment in our infrastructure revolution.
"HS2 is the most significant expansion to our national railways in a generation - transforming connectivity between our towns and cities and vastly increasing the capacity of our rail network.
"By proceeding full steam ahead, we are delivering on our commitment to unite and level up the country.
"The construction of Phase 2a will support thousands of jobs and create opportunities for local businesses as we build back better."
Transport Secretary Grant Shapps said: "Whatever your view of this project, HS2 is now a reality - heading north, creating jobs and building a brighter future for our country.
"This vital project is at the heart of the Government's commitments to build back better from the pandemic, tackle the North-South divide and drive growth across the country.
"The signing of the Phase 2a Bill into law is an historic milestone for this ambitious project, which is already creating and supporting thousands of jobs across the UK.
"I look forward to seeing spades in the ground to get this section built and deliver the benefits of high-speed rail to the North as swiftly as possible."