Shannon Murray, 32, uses her wheelchair as a prop in the photo shoot alongside standing models and designer Ben de Lisi.
The actress and model has been modelling for 14 years but this is a first for a High Street store, which she said is another small step towards inclusion for the disabled.
"I hope the images challenge a few misconceptions about disability; it's been a long time coming", Shannon told the Daily Mail.
The campaign is promoting Ben de Lisi's new fashion range for the relaunched Principles brand in Debenhams.
The campaign has been partnered up with Channel 4's TV show How To Look Good Naked, where stylist Gok Wan encourages the fashion industry to take on disabled women.
Debenhams also included a size 16 model in the campaign, along with a 5ft 4 model and a size 10 model to show diversity.
The shoot will appear in the Oxford Street branch window in London.
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