The 'I Dreamed A Dream' star took to the stage at Newcastle's Theatre Royal, where fans from all over the world had come to support the new production, in which Elaine C Smith is playing Boyle.
Boyle herself will make a cameo after the curtain call most nights, performing the Les Misérables track which propelled her to fame on Britain's Got Talent.
During the performance, one American fan shouted: "We love you!" to which Boyle responded: "I love you too, see you outside."
Based on her autobiography The Woman I Was Born to Be, the musical tells the story from Boyle's birth, her time at school, being bullied for her learning difficulties, her decision to perform on stage for Simon Cowell in 2008 and subsequent struggle with fame.
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American supporter Marie Sheahan Brown praised Smith - who also co-wrote the story - for her role: "I could watch it again, it was fabulous. Elaine did a marvellous job and she can really sing.
"There are people from 15 countries here, and from 20 states in the US. She speaks to a lot of people's hearts. It's not only her stunningly glorious voice, it's her as a person."
Critics have so far given the production a warm welcome, with Dominic Cavendish from The Telegraph writing that the five-star musical is "a delight that deserves to go far, and fast, as she has done".
The Susan Boyle Musical: I Dreamed A Dream will visit 11 UK and Irish cities over the coming months, with Boyle expected to make a similar curtain call appearance at most performances.