Thornton in Milton Keynes previously closed in 2019, but plans are to close their other 61 stores and move to online only.
The company said its decision, which was now the subject of consultation with employees, would affect 603 workers though it was yet to rule out the possibility of redeploying some of those affected.
Thorntons said it was based not only on the impact of COVID-19 lockdowns over the past year but factors related to the pandemic across the retail sector.
Adam Goddard, the company's retail director, said it was clear Thorntons had to "evolve".
He said in a statement: "Changing dynamics of the high street, shifting customer behaviour to online, the ongoing impact of COVID-19 and the numerous lockdown restrictions over the last year - especially during our key trading periods at Easter and Christmas - has meant we have been trading in the most challenging circumstances.
"Unfortunately like many others, the obstacles we have faced and will continue to face on the high street are too severe and despite our best efforts we have taken the difficult decision to permanently close our retail store estate."
Thorntons, which has been owned by Italian firm Ferrero since 2015, said online sales would be a key part of its strategy after it witnessed a 71% increase in net sales via digital channels over the past year.
It also committed to its Alfreton factory and investment in its grocery supply business.
Thorntons is among a string of big names to go online-only in recent months.
The brands within Sir Philip Green's former Arcadia empire, including TopShop, and Debenhams have been taken over by ASOS and Boohoo this year.
A Sky News tracker suggests retail has suffered the most damage in terms of jobs lost among big names since the crisis began.
