The "short, sharp" lockdown will begin on Friday 23 October at 6pm until Monday 9 November.
Household mixing will be banned across all settings and Welsh residents have been urged to stay at home.
Non-essential retail and leisure businesses will also have to close, with residents urged to work from home wherever they can.
An extra economic resilience fund of almost £300m has been created, some of which will go to businesses impacted by the "firebreak" lockdown.
This will include a one-off payment up to £5,000 for hospitality businesses.
The Welsh Government will set out more details about the economic support package for businesses this week, the First Minister said.
Drakeford said: "There are no easy choices in front of us as the virus spreads rapidly in every part of Wales."
Although large parts of the nation have already been under harsh restrictions on socialising and travelling for a number of weeks, ministers agreed more was needed to curb the virus and protect the NHS.
"It will have to be sharp and deep in order to have the impact we need," Drakeford said at a press conference.
The Welsh Government has already moved to ban tourists travelling to the country from coronavirus hotspots in England where second or third tier measures are in place.
UKHospitality chief executive Kate Nicholls tweeted to say this would hit the wider hospitality and leisure economy and it was crucial adequate support was introduced.
She said: "This is likely to affect more than just pubs and restaurants - hotels, holiday parks, attractions - hitting Welsh tourism hard over half term so vital that the sector and supply chain is supported through another winter."
This is likely to affect more than just pubs and restaurants - hotels, holiday parks, attractions - hitting Welsh tourism hard over half term so vital that the sector and supply chain is supported through another winter https://t.co/A5PQXtayeP— Kate Nicholls (@UKHospKate) October 19, 2020
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