Chairman Tim Martin said he hoped it would be the first of many such pubs on Britain's motorway network. It comes amid a Government consultation on lifting restrictions on alcohol sales at motorway service areas.
Wetherspoon's has been granted permission for a 24-hour bar and restaurant at junction 2 of the M40 at Beaconsfield, Buckinghamshire, which will have a licence to serve alcohol fom 8am to 1am seven days a week.
The pub, which has yet to be given a name, is expected to be open by Christmas.
A spokesman played down the idea that the opening was likely to lead to drink-driving, saying: "We don't see any problem."
The spokesman said much of Wetherspoon's sales came from food and that it also served non-alcoholic and hot drinks.
"We believe the majority of people that use the pub to drink will be people that aren't driving - coach parties or people travelling with others. We won't be asking them whether they are driving. It's up to them."
The company said it had received no objections to the plans after meeting representatives from Thames Valley Police and South Buckinghamshire District Council. It said the £2 million development with service area operator Extra would create 50 jobs.
Mr Martin said: "We are looking forward to opening our first licensed bar and restaurant on the motorway network. The company has always been innovative and this is an exciting new development for us. Hopefully it will be the first of many Wetherspoons on the motorway."
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