Anthony "Tick" Belrose, who performs as Mitzi Del Bra, is a drag queen from Sydney presented with an opportunity to showcase his talent at Lasseters Hotel Casino Resort. This venue is managed by his estranged wife, Marion. To make his dreams a reality, he convinces his closest friends—Bernadette Bassenger, a transgender woman recently mourning her partner, and Adam Whitely, an exuberant younger drag queen known as Felicia Jollygoodfellow—to embark on a four-week performance tour at the casino. They set off in a large tour bus, affectionately named "Priscilla, Queen of the Desert," embarking on an adventure through the heart of Australia.
As they traverse the breathtaking yet desolate landscapes bordering the Simpson Desert, the trio encounters various characters along the way. They experience an uplifting moment performing for an amicable group of Aboriginal Australians at a corroboree, however, they are also met with the harsher realities of rural Australia in towns like Broken Hill, facing homophobic slurs and even violence, as their bus is defaced with hateful graffiti.
When misfortune strikes and the bus breaks down in the vast desert, Adam dedicates an entire day to repainting it lavender, turning the act of covering the graffiti into a form of self-expression. Their travels bring them to meet Bob, a middle-aged mechanic whose recent heartbreak has left him seeking companionship. He finds solace with the group when his wife, Cynthia, departs from him. Just before arriving in Alice Springs, Tick discloses a significant secret: Marion is not just his estranged wife—they have never divorced. His journey back is partly a gesture to support her.
Their adventures take a darker turn in Coober Pedy, a remote opal-mining town, where Adam narrowly escapes serious injury from a gang of homophobes, thanks to the brave interventions of Bob and Bernadette. The harrowing experience deepens their bonds, allowing them to better understand each other's struggles. As tensions ease among them, they enjoy a shared ambition to scale Kings Canyon dressed in full drag, a long-cherished dream of Adam.
Upon their arrival at the hotel, Tick learns that he has an eight-year-old son, Benjamin, who he hasn’t seen in years. The thought of revealing his identity as a drag queen and gay father fills him with anxiety. To his surprise, he discovers that Benjamin is already aware and accepts him wholeheartedly. This revelation adds complexity to their reunion, particularly when Benjamin mentions that Marion has also had her own experiences with relationships outside the norm.
As their contract with the resort concludes, Tick and Adam return to Sydney, taking Benjamin along so they can forge a deeper connection. Meanwhile, Bernadette chooses to stay at the resort, developing her bond with Bob as he contemplates working there after a newfound closeness with her.
A whimsical element is revisited in the film's post-credit scene, wrapping up the narrative with a light-hearted twist: the dummy attached to a kite that was introduced earlier finds its way to a temple in Tibet, where a monk discovers it, offering a humorous capstone to their extraordinary journey.
