Three years on from being denied the continental crown on spot-kicks, they had to fight their demons from 12 yards to continue their quest to go one better in Germany.
Bukayo Saka cancelled out Breel Embolo's opener to take the quarter-final to extra-time and onto penalties after it ended 1-1, with the England star converting to bury the ghosts of his Euro 2020 final miss.
But Pickford was the star as he saved Manuel Akanji's penalty, with Trent Alexander-Arnold wrapping up a 5-3 triumph to spark bedlam in Dusseldorf and seal a semi-final spot.
It was a dramatic end to an edgy encounter and England's first shoot-out win since beating the Swiss in the Nations League third-placed play-off five years ago in Portugal.
Pickford was the hero then, just as he was on Saturday night as Gareth Southgate's 100th match ended with a victory that sets up a Dortmund clash against Turkey or the Netherlands on Wednesday.
Switzerland stuck with the same side that knocked out holders Italy as Southgate made one enforced change and a big switch in system.
Ezri Konsa replaced suspended centre-back Marc Guehi and formed part of a back three, with eyebrows raised at the decision to deploy Saka as right wing-back rather than on the opposite side.
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We are fragile but we cannot overreact-Pep
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