Ayola last acted opposite Sheen 40 years ago when they were both teenagers, as part of a National Youth Theatre of Wales residency.
She said: “[Michael and I] have got some unfinished business, which is perfect to play these two married people, who’ve got a lot going on.”
The Holby City actor, who grew up in Ely, Cardiff, said Owain Glyndŵr was only known to her as the name of a pub in the city centre until she was an adult, despite him being “an integral part of Welsh history”.
Welsh history is now a compulsory part of the Curriculum for Wales.
Graeme Farrow, creative director at the Wales Millennium Centre, said: “I think producing ambitious theatre on this scale is even more of a gamble than ever because the costs have gone up, the financial risks are greater than ever, but with this we knew the risk was worth taking, it’s a brilliant play.
“The response has been sensational. It’s going to be pretty much full every night if not sold out for the whole of its run which is a huge relief, but now it’s all about putting on the show.”
Owain & Henry runs at the Wales Millennium Centre from 5 November until 28 November.
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