Royal Assent has been given for Phase 2a of the budget-busting line.
It comes one year after Boris Johnson signed off on the controversial scheme, which has drawn widespread criticism over spiralling costs and damage caused to the environment.
Environmental works are set to start this year, with building work beginning in 2024. It is estimated to cost around £14 billion, on top of £45bn for the first phase of the line from London to Birmingham.
No decision has yet been made on Phase 2b from Birmingham to Leeds.
It comes after the West Midlands Combined Authority launched its HS2 Growth strategy, which claims the new line could generate 175,000 jobs and £20bn investment in the region.
Transport Secretary Grant Shapps said the project was "now a reality" and would help to "tackle the North-South divide and drive growth across the country".
West Midlands Mayor Andy Street, said: "HS2 was always going to be a game-changer for the West Midlands, but the jobs and economy aspect of the scheme has taken on even more significance in light of the pandemic.
"HS2 will be a key anchor of the region's recovery plans, with our latest research suggesting the knock-on effect of HS2 could eventually generate 175,000 jobs and more than £20bn of investment.
"These are extraordinary numbers, which shows just how critical it was to win the argument for HS2. With thousands in the West Midlands already employed and working on the project, HS2 is making a critical difference to people's livelihoods right now."
Sara Williams, CEO of Staffordshire Chamber of Commerce, also welcomed the news.
She said: “HS2 brings potential benefits for Staffordshire businesses, both now and in the future. Extending the high speed line northwards will generate thousands of contract opportunities for local businesses of all sizes and their involvement will provide a vital boost for the Staffordshire economy in the years ahead.”
Maria Machancoses, director of Midlands Connect, hailed the “historic milestone” and called for construction work to start “as soon as possible”.
“While Phases One and 2a are moving ahead apace, and have created thousands of highly-skilled jobs, apprenticeships and unprecedented regeneration, it is essential that an decision is made on the scope of Phase 2b of the project, especially the Eastern Leg of the route between Birmingham, the East Midlands, Chesterfield, Sheffield and Leeds.
"Any further delay will cause uncertainty at a time where business confidence and job security have been shaken by Covid-19. We in the Midlands and North are clear, we need the whole of the HS2 network to be delivered, in full.”
HS2 Minister Andrew Stephenson said: “Once built, HS2 will be a catalyst for regeneration for the West Midlands, Staffordshire and Cheshire, providing benefits for the great towns and cities across these regions for decades to come.”
John Spellar, the Labour MP for Warley, has called for the entire project to be reassessed, arguing that people's work patterns had changed due to the Covid pandemic.
Lichfield's Conservative MP Michael Fabricant said persisting with the scheme – which is expected to cost well over £100bn – was "throwing good money after bad".
More than 100 ancient woodlands, including several in Staffordshire, are set to be destroyed to make way for the line.