At SportsCenter Scott was frequently teamed with fellow anchor Rich Eisen. He became well known for his use of unique catch phrases, following in the SportsCenter tradition begun by Dan Patrick and Keith Olbermann, such as "holla at a playa when you see him in the street!", "call him butter, he's on a roll" and "Boo Yah!" and also "as cool as the other side of the pillow." He was parodied on Saturday Night Live by Tim Meadows and Finesse Mitchell.
Scott was injured when hit in the face by a football during a New York Jets mini-camp on April 3, 2002, while filming a special for ESPN. He underwent surgery that night and was out of work for a few months. Because of the accident, he has ptosis, or drooping of the eyelid.
Scott had an emergency appendectomy in Pittsburgh after becoming ill while covering the Pittsburgh Steelers–Miami DolphinsMonday Night Football game on November 26, 2007. The surgery also discovered a malignancy that required an additional surgery to remove possibly cancerous tissue. He returned a month later and continued on-air broadcasting during recommended preventive chemotherapy. ESPN President George Bodenheimer said "Stuart is approaching this fight with the same passion and energy we see on air... He knows he has our full support and we look forward to the day where this is all behind him."
In 2011, it was revealed that Scott was again battling cancer. The disease entered remission in early 2012, but Scott was again diagnosed with cancer on January 14, 2013.
Scott was honored at the ESPYS on July 16, 2014, with the Jimmy V Award for his ongoing, inspirational fight against cancer. He shared that he had four surgeries in seven days in the week prior to his appearance, when he was suffering from liver complications and kidney failure.