St. Clair first rose to prominence when she won the title of Miss Gay Indiana in 2016. She was revealed as one of fourteen contestants on the tenth season of RuPaul's Drag Race before the official cast was announced due to getting arrested for a DUI violation. She is the first contestant from Indiana to compete on the show. She was the sixth contestant eliminated on a lipsync to Diana Ross' "I'm Coming Out", losing to The Vixen, and placing ninth.
St. Clair's grand finale dress was designed by Project Runway alumnus Mondo Guerra. After the show, she walked for Guerra's collection at FashioNXT in October 2018.
St. Clair released a follow-up single, "Call My Life", with a music video on June 26, 2018. Her seven-track debut album of the same name was released three days later.Drag Race alumna Alaska is featured on the album's sixth track, "America's Sweetheart". The album peaked at number one of the BillboardDance/Electronic Sales Chart. A remix EP of the "Call My Life" single was released on August 10, 2018. It features Dave Audé, Chris Cox, DrewG., Hector Fonseca, Zambianco and Ralphi Rosario. She released her third single, "Irresistible" with a music video on October 25, 2018. Blair St. Clair released her single "Easy Love" on July 12, 2019. 
The first part of St Clair's drag name came from the character Blair in Gossip Girl while the second part was suggested by her mother after she had passed St. Clair Street in downtown Indianapolis.
St Clair was raped at a college party, which she shared on RuPaul's Drag Race. In 2018, Drag Race winner Bianca Del Rio controversially made a joke about the rape at one of her comedy sets. Del Rio received backlash from fans and fellow queens including St. Clair herself.