Duff, who has won numerous awards for her theatre work, will revive her involvement in the epic James Plays series when the next instalment tours the country in the autumn.
The new show, which will be launched in Edinburgh in October, will be based on the true story of two young African women – known as the "Moorish lassies" – who found themselves at the heart of elite Scottish society during the reign of James IV.
Also returning to play the role of the Stewart king will be River City and Anna and the Apocalypse star Daniel Cahill, who also starred in the original trilogy and played the future James IV in the final part.
Duff, who will play Dame Dounteboir, and Cahill will be reunited with writer Rona Munro and director Laurie Sansom for James IV, eight years after the original trilogy was premiered at the Edinburgh International Festival.
Danielle Jam and Laura Lovemore have been cast as Ellen and Anne, the new arrivals in the king’s court, in James IV, which will also feature Ewan Black, Malcolm Cumming, Keith Fleming, Sarita Gabony, Thierry Mabonga, Samuel Pashby and Gameli Tordzro.
It was announced last year that Munro was working on another three James Plays, the first of which will premiere at the Festival Theatre in Edinburgh this year.
Capital Theatres, which runs the venue, has joined forces with Glasgow-based theatre company Raw Material to produce the new instalments.
Duff, who played Isabella and Annabella in the original trilogy, said: “I was delighted to find out the brilliant Rona Munro had worked her magic and created James IV.
"I was given a tantalising glimpse of the script when Laurie Sansom invited me to workshop the piece in May last year.
"Being back on the Festival Theatre stage during that week reminded us of the extraordinary legacy and impact The James Plays had, not only personally, but on audiences when it toured nationally and internationally.
“It was an extraordinary part of my life and I was transported once again with Rona’s storytelling and forensic detail.
“As ever her wit shines through and she is always revealing the strength of her female characters.
“The partnership and trust she has with Laurie Sansom is evident and so important in bringing all the elements together. I just can’t wait to be back in the rehearsal room and be with the wonderful team who are ready to bring their creativity and expertise to the next exciting chapter of Scotland’s history. I feel sure the audience are ready too.”
Cahill said: “Rona’s work has always meant a lot to me, as indeed it does to every young Scottish actor, and to be a part of Laurie’s magnificent vision was a real honour.
“To be revisiting the character of James who I played when we were both nearly ten years younger feels like something special.
"I’ve still got such vivid memories of what he went through as a kid and I feel that with this bridge to the original trilogy, the momentum of the plays is going to be carried through into this next chapter.”