Oakley had originally joined the cast last week, covering the lead role of Jenna due to cast illness.
After flying in from the States at a moment's notice, Oakley made her West End debut in the production having previously performed the role on tour in North America.
But she found her talents called upon again on Monday night while she was sat in the audience watching the show.
Oakley took over the role for the second act after Lucie Jones was taken ill.
Audience member @lucyellasmith wrote on Twitter: "Two wonderful Jenna’s for the price of one! @WaitressLondon 🥧 Congratulations @desioakley & get well soon @luciejones1 💙"
Meanwhile @whatcomesourway shared a clip of the curtain call and commented: "Lucie Jones and Desi Oakley are two amazing, amazing people. That’s all I'm saying."
— lorna 🥧 (@whatcomesourway) January 20, 2020
Just before taking over the role mid-show, Oakley had taken to social media to share a picture of herself enjoying a well earned glass of champagne from the comfort of the audience.
"I've taken a deep relaxing breath for the first time in days," she captioned the picture on Instagram.
Based on the film of the same name, Waitress tells the story of Jenna a waitress and expert pie-maker who dreams of a way out of her small town and rocky marriage.
It was announced recently that Waitress will close in London's West End on July 4 2020 before heading out on a first UK tour.
Before then, Sara Bareilles - who composed the musical's score - will appear in the cast for a limited time from January 27 together with Gavin Creel.
The pair, who both previously starred in the show on Broadway, will take on the roles of Jenna and Dr Pomatter through to March 7.