Around 600,000 retail, hospitality and leisure sites will be able to claim a one-off grant of up to £9,000, the Government has announced.
The payments will cost the Treasury £4.6 billion and are aimed to help support the high street as new lockdown measures announced on Monday take hold.
Chancellor Rishi Sunak also announced a further £594 million for local authorities and devolved administrations to support businesses not eligible for the grants.
The Scottish Government will receive £375 million, the Welsh Government £227 million and the Northern Ireland Executive £127 million.
Mr Sunak said: "The new strain of the virus presents us all with a huge challenge – and whilst the vaccine is being rolled out, we have needed to tighten restrictions further.
"Throughout the pandemic we've taken swift action to protect lives and livelihoods and today we're announcing a further cash injection to support businesses and jobs until the spring.
"This will help businesses to get through the months ahead – and crucially it will help sustain jobs, so workers can be ready to return when they are able to reopen."
The payments will be based on the size of each store, pub, cafe or hotel tied into the business rates typically paid by each business. The smallest sites will be able to claim up to £4,000 and medium-sized ones £6,000.
However, the Chancellor stopped short of extending the business rates holiday, which ends in April, despite calls from retail and hospitality leaders for such a move.
Other noticeable absences being called for by business groups and unions include a VAT cut and improvements to sick pay or support for working parents.
On Monday night Helen Dickinson, chief executive of the British Retail Consortium, said: "The biggest difference the Government can make is to extend business rates relief from April for those hardest hit by repeated lockdowns."
According to real estate specialists Altus Group, 401,690 non-essential shops, 64,537 pubs/restaurants, 20,703 personal care facilities and 7,051 gyms and leisure centres are now closed.
The new one-off grants come in addition to grants worth up to £3,000 for closed businesses, and up to £2,100 per month for impacted businesses once they reopen.
The Government has already provided £1.1 billion of discretionary funding for local authorities, extended the furlough scheme until April and taxpayer-backed business loans until March.