Penny Mordaunt and Grant Shapps are among a number of Conservative cabinet ministers who have lost their seats in quick succession amid a Tory bloodbath.
The humiliating blows one after the other come as Sir Keir Starmer is set to be swept to power by a landslide Labour victory.
Labour is predicted to have a 170-seat majority in the Commons, with the Tories reduced to just 131 seats - their lowest number of MPs on record.
If the results indicated by an exit poll are accurate, Rishi Sunak's term as Prime Minister will end in electoral disaster and could see him resign.
Although Mr Sunak managed to hold on to his Richmond and Northallerton sea and Chancellor Jeremy Hunt narrowly won his Godalming & Ash seat, eight members of his Cabinet members have so far been defeated.
Ms Mordaunt, the Conservative leader of the House of Commons who lost her seat of Portsmouth North, said in defeat: 'To anyone who is disappointed, democracy is never wrong.'
Defence Secretary Mr Shapps, who lost his Welwyn Hatfield seat, paid tribute to the 'selfless courage of the men and women of this country who serve in our armed forces'.
Chief whip Simon Hart, Education Secretary Gillian Keegan, Justice Secretary Alex Chalk, Culture Secretary Lucy Frazer and Veterans Minister Johnny Mercer have also lost their seats.
Although Mr Sunak held his seat, he said: 'The Labour Party has won this general election, and I have called Sir Keir Starmer to congratulate him on his victory.
'I will now head down to London, where I will say more about tonight's result, before I leave the job as Prime Minister, to which I have given my all.'
'I will now head down to London, where I will say more about tonight's result, before I leave the job as prime minister, to which I have given my all.'
Follow MailOnline's coverage as we look at the Tory big guns desperately clinging on to avoid a Portillo moment - a reference to Tory cabinet minister Michael Portillo losing a safe Tory seat in Labour's 1997 landslide.