The Bet365 founder and her family, who are worth £7.166bn, stumped up an eye-watering £573million tax bill.
Glenn Gordon, whose distillery empire has netted his family a £3.186bn fortune, came in second with tax liabilities of £436.4million.
Sir James Dyson also featured on the Sunday Times Tax List 2021 in sixth place after pouring £115million into the Treasury coffers - £12million more than the year before.
The Brexiteer vacuum tycoon, who topped the 2020 rich list with his £16.2billion fortune, announced he was relocating Dyson s head office to Singapore in 2019.
Celebrities including JK Rowling and Ed Sheeran were also ranked in the top 50 taxpayers, who on average paid less than the year before.