Boots will sack more than 4,000 employees - about 7pc of its workforce - and close almost 50 Opticians stores in response to a dramatic decline in footfall following the coronavirus outbreak.
The Walgreens-owned chemist said it was taking "decisive action to mitigate the significant impact that Covid-19 has had on the business".
Although Boots remained open during lockdown, the number of customers fell significantly and its profitable beauty and fragrance counters were closed.
More than 100 larger stores in city centres, stations and airports were closed, as were most Boots Opticians practices during lockdown.
That helped to almost halve like-for-like sales for the three months to the end of May compared with the same period last year, while sales dipped by almost three quarters for Boots Opticians.
"Restrictions are beginning to lift, but with an uncertain economic outlook, it is anticipated that the high street will take considerable time to recover," the retailer said.
Boots UK boss Sebastian James said: “The proposals announced today are decisive actions to accelerate our transformation plan, allow Boots to continue its vital role as part of the UK health system, and ensure profitable long-term growth.
"We recognise that today’s proposals will be very difficult for the remarkable people who make up the heart of our business, and we will do everything in our power to provide the fullest support during this time.”
The decline in UK sales contributed to a sales hit of up to $750m (£584m) for Walgreens Boots Alliance, which is taking a $2bn impairment charge.
The company posted a $1.7bn loss for the three months to the end of May despite sales remaining flat at $34.6bn.
Chief executive Stefano Pessina said: “Prior to the pandemic our financial performance for fiscal 2020 was on track with our expectations. However, this unprecedented global crisis led to a loss in the quarter as stay-at-home orders affected all of our markets."
Walgreens bought a 45pc stake in Boots in 2012 and two years later acquired the remainder in a £9bn deal.
Walgreens Boots Alliance has been assembled by Stefano Pessina over a decade and has almost 19,000 stores in 11 countries with annual revenues of close to $140bn before the pandemic.
Mr Pessina owns 16pc of the group's shares and was rumoured to be holding talks late last year with private equity groups over taking the company private.