The singer, 27, wrote the ballad just four days before her near-fatal overdose in July 2018. After receiving a standing ovation from the audience, Lovato took to social media to reflect on the moment.
"What an unbelievable night. My first time back on stage in almost 2 years," she described. "So emotional for me. Thank you all for the love, support and for sharing this moment with me. I love you all."
The lyrics to "Anyone" touched upon Lovato's state of mind during that period.
"I tried to talk to my piano / I tried to talk to my guitar / Talked to my imagination / Confided in to alcohol / I tried and tried and tried some more / Told secrets 'til my voice was sore / Tired of empty conversation / Cause no one hears me anymore," Lovato began.
"A hundred million stories / And a hundred million songs / I feel stupid when I sing / Nobody's listening to me / Nobody's listening / I talked to shooting stars / But they always get it wrong / I feel stupid when I pray / So, why am I praying anyway? / If nobody's listening," she continued.
"Anyone, please send me anyone / Lord, is there anyone? / I need someone / Anyone, please send me anyone / Lord, is there anyone? / I need someone."
Some of Lovato's famous friends reacted to her triumphant return to music. Her childhood friend Selena Gomez posted a message on her Story. “I wish there were words to describe how beautiful, inspirational and DESERVED this moment was. Demi I’m so happy for you. Thank you for your courage and bravery,” Gomez wrote.
While Lovato's manager Scooter Braun said, “No words. So proud of u."
And Sam Smith wrote, "I am in tears. That is singing. That is heart and that is the truth."
Lovato is also set to perform the national anthem before this year's Super Bowl on Feb. 2. Shakira and Jennifer Lopez will perform the halftime show.