Marked by a construction opening ceremony on Wednesday, December 9, the centre at University College London Hospital is due for completion in 2019, while Christie Cancer Centre in Manchester is scheduled for completion in 2018.
Alongside these two new facilities, in the private sector, Proton Partners International plan a Newport centre that will offer some NHS treatments.
Proton beam therapy garnered world-wide attention last year, with the case of five-year-old Aysha King, whose parents took him abroad for treatment against the advice of his doctors.
Currently, proton beam therapy is unavailable in the UK and can cost upwards of £75,000 in foreign clinics.
The NHS facilities aim to reduce this cost to £40,000 per patient.
Sir Robert Naylor, chief executive of UCLH, told the BBC: "To have work under way on this long-awaited centre is tremendous news.
"This will be a game-changer for NHS patients who will benefit from local access to advanced treatments."
Figures suggest that currently between 120-140 patients a year have to go to foreign clinics for treatment funded by the NHS.