HS2 Ltd and its contractors are expected to recruit for the roles in the coming years to build Phase One of the controversial route, which runs from London to Birmingham.
The project has now moved on from enabling and preparatory works to focus on the construction of the railway.
Boris Johnson described the line as being "at the heart of our plans to build back better", and said the jobs created would offer people a path back into work after the pandemic.
"As the spine of our country’s transport network, the project will be vital in boosting connectivity between our towns and cities," the Prime Minister added.
"But HS2’s transformational potential goes even further. By creating hundreds of apprenticeships and thousands of skilled jobs, HS2 will fire up economic growth and help to rebalance opportunity across this country for years to come."
Around 22,000 construction jobs will be created to build Phase One of HS2. This includes 7,000 jobs in the West Midlands, where Balfour Beatty is the main contractor.
Mark Thurston, CEO of HS2 Ltd said: "We are already seeing the benefits that building HS2 is bringing to the UK economy in the short term, but it’s important to emphasise how transformative the railway will be for our country when operational.
"With the start of construction, the reality of high speed journeys joining up Britain’s biggest cities in the North and Midlands and using that connectivity to help level up the country has just moved a step closer."
Transport Secretary Grant Shapps today claimed HS2 is being built to last “150 years” as he defended its continuing need.
The pandemic has led to many more people working from home, with demand for trains more than halved, but speaking ahead of a “shovels in the ground” event for HS2 at an undisclosed location, Mr Shapps insisted it is wrong to think the virus has made the high-speed railway unnecessary.
He told BBC Radio 4’s Today programme: “We’re not building this for what happens over the next couple of years or even the next 10 years.
“We’re building this – as with the west coast and east coast mainlines – for 150 years and still going strong.
“So I think the idea that – unless we work out a way of teletransporting people – that we won’t want a system to get people around the country… is wrong.”
Prime Minister Boris Johnson said the high-speed railway will create thousands of jobs and create vital links between urban areas.
He said: “HS2 is at the heart of our plans to build back better – and with construction now formally under way, it’s set to create around 22,000 new jobs.
“As the spine of our country’s transport network, the project will be vital in boosting connectivity between our towns and cities.”
All revenue and cost risks from existing rail franchises were transferred to the UK, Scottish and Welsh governments in March to ensure services continued despite the collapse in demand caused by the coronavirus lockdown.
This has cost taxpayers at least £3.5 billion.
The Government-commissioned Oakervee Review warned last year that the final bill for HS2 could reach £106 billion at 2019 prices.
Despite it running tens of billions of pounds over budget and several years behind schedule, the PM gave the green light for the railway in February.
The project was given a revised budget and schedule as part of his decision.
Two months later, ministers gave the go-ahead for it to enter the construction phase between London and the West Midlands.
Work will begin with the biggest engineering challenges – such as the stations and tunnels – followed by the main viaducts and bridges.
Most activity this year will be focused on HS2’s city centre stations and major construction compounds, including at Old Oak Common, west London, and Calvert, Buckinghamshire.
HS2 Ltd chief executive Mark Thurston said: “This is a hugely exciting moment in the progress of HS2. After 10 years of development and preparatory work, today we can formally announce the start of full construction, unlocking thousands of jobs and supply chain opportunities across the project.
“We are already seeing the benefits that building HS2 is bringing to the UK economy in the short term, but it’s important to emphasise how transformative the railway will be for our country when operational.
“With the start of construction, the reality of high-speed journeys joining up Britain’s biggest cities in the North and Midlands and using that connectivity to help level up the country has just moved a step closer.”