The pair, who play Weatherfield's Stella Price and Ken Barlow, will team up together in a live broadcast on August 20, while their co-star Kym Marsh (Michelle Connor) will appear with fiancé Jamie Lomas, better known as Hollyoaks' Warren Fox, the following evening.
Emmerdale's Mark Charnock and Dominic Brunt (Marlon Dingle and Paddy Kirk) will also play the game together, as will on-screen mother and son Lucy Pargeter and Danny Miller (Chas Dingle and Aaron Livesy).
Hollyoaks' McQueen duo Gemma Merna and Jennifer Metcalfe - Carmel and Mercedes in the Channel 4 show - are also taking part.
Danny Miller said of the challenge: "I've grown up watching Chris Tarrant on Who Wants To Be A Millionaire? so getting into the hotseat is going to be very daunting."
Meanwhile, Mark Charnock said: "It's such an iconic show and I've always wanted to do it, but I can imagine Dominic and I will be clinging to each other, panicking, going red and sweating!"
Further soap star pairings are expected to be announced later this month.
> Chris Tarrant: 'Who Wants To Be A Millionaire should be open to the public'
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