William Hill plans to close 700 of its 2,300 British betting shops, putting about 4,500 jobs, a third of its workforce, at risk.
The planned closures come after the UK government cut the maximum stake on fixed-odds betting terminals to tackle problem gambling.
The cut in the maximum stake to £2 followed complaints that the machines, which had allowed gamblers to bet up to £100 every 20 seconds, were highly addictive and allowed players to rapidly lose large sums of money.
William Hill had last year warned that about 900 shops could be shut as a result of the change.
It said today that it had suffered a significant fall in gaming machine revenues since the change was introduced in April, adding that the closures were likely to begin before the end of the year.
The UK government had rejected industry suggestions when it brought in the stake cut that such a big reduction in the maximum stake could cost thousands of jobs.
Rival GVC Holdings has warned the restrictions would lead to the closure of up to 1,000 shops and cut its 2019 core profit by about £135m.
William Hill's retail business has about 2,300 licensed betting shops and is its largest division, generating 56% of its net revenue in 2018 and employing around 12,500 people in Britain, which accounts for about 90% of its business.
The company said in January that it would remodel its retail business after performance at it was hit by tighter regulations, particularly on lucrative FOBTs.
In May William Hill, which has betting shops, sports books and online and mobile channels in eight countries, said that UK retail gaming net revenue was down 15%.
William Hill's chief executive Philip Bowcock had earlier said that the introduction of the £2 stake limit was in line with expectations and that the company was confident in its plan to manage the change.
The company has had no shops in the Republic of Ireland since 2011.