Scott was born Stuart Orlando Scott in Chicago, Illinois on July 19, 1965 to O. Ray and Jacqueline Scott. When he was 7, Scott and his family moved to Winston-Salem, North Carolina. Scott had a brother named Stephen and two sisters named Susan and Synthia.  He attended Mount Tabor High School for 9th and 10th grade and then completed his last 2 years at Richard J. Reynolds High School in Winston-Salem—graduating in 1983. In high school, he was a captain of his football team, ran track, served as vice president of the student government and was the Sergeant at Arms of the school’s Key Club. Scott was inducted into the Richard J. Reynolds High School Hall of Fame during a ceremony on February 6, 2015. The ceremony took place during the Reynolds/Mt. Tabor (the two high schools that Scott attended) basketball game.  He attended the University of North Carolina at Chapel Hill. He was a member of Alpha Phi Alpha fraternity and was part of the on-air talent at WXYC. While at UNC, he also played wide receiver and defensive back on the club football team. In 1987, Scott graduated from the University of North Carolina with a Bachelor of Arts in speech communication. In 2001, Scott gave the commencement address at UNC where he implored graduates to celebrate diversity and recognize the power of communication.

Following graduation, Scott worked as a news reporter and weekend sports anchor at WPDE-TV in Florence, South Carolina from 1987 until 1988. Scott came up with the phrase “cooler than the other side of the pillow” while working his first job at WPDE. After this, Scott worked as a news reporter at WRAL-TV 5 in Raleigh, North Carolina from 1988 until 1990. WRAL Sports anchor Jeff Gravley recalled there was a “natural bond” between Scott and the sports department. Gravley described his style as creative, gregarious and adding so much energy to the newsroom. Even after leaving, Scott still visited his former colleagues at WRAL and treated them like family.  From 1990 until 1993, Scott worked at WESH, an NBC affiliate in Orlando, Florida as a sports reporter and sports anchor. While at WESH, he met ESPN producer Gus Ramsey, who was beginning his own career. Ramsey said of Scott: “You knew the second he walked in the door that it was a pit stop, and that he was gonna be this big star somewhere someday. He went out and did a piece on the rodeo, and he nailed it just like he would nail the NBA Finals for ESPN.” He earned first place honors from the Central Florida Press Club for a feature on rodeo.

Al Jaffe, ESPN’s vice president for talent, brought Scott to ESPN2 because they were looking for sportscasters who might appeal to a younger audience. Scott became one of the few African-American personalities who was not a former professional athlete. His first ESPN assignments were for SportsSmash, a short sportscast twice an hour on ESPN2’s SportsNight program. After Keith Olbermann left SportsNight for ESPN’s SportsCenter, Scott took his place in the anchor chair at SportsNight. After this, Scott was a regular on SportsCenter. At SportsCenter, Scott was frequently teamed with fellow anchors Rich Eisen, Steve Levy, Kenny Mayne, Dan Patrick, and others. Scott was a regular in the This is SportsCenter commercials.

In 2002, Scott was named studio host for the NBA on ESPN. He became lead host in 2008, when he also began at ABC in the same capacity for its NBA coverage, which included the NBA Finals. Additionally, Scott anchored SportsCenter’s prime-time coverage from the site of NBA post-season games. From 1997 until 2014, he covered the league’s finals. During the 1997 and 1998 NBA Finals, Scott did one-on-one interviews with Michael Jordan. When Monday Night Football moved to ESPN in 2006, Scott hosted on-site coverage, including Monday Night Countdown and post-game SportsCenter coverage. Scott previously appeared on NFL PrimeTime during the 1997 season, Monday Night Countdown from 2002–2005, and Sunday NFL Countdown from 1999–2001. Scott also covered the MLB playoffs and NCAA Final Four in 1995 for ESPN.  Scott appeared in each issue of ESPN the Magazine, with his Holla column. During his work at ESPN, he also interviewed Tiger Woods, Sammy Sosa, President Bill Clinton and President Barack Obama during the 2008 presidential campaign. As a part of the interview with President Barack Obama, Scott played in a one-on-one basketball game with the President.  In 2004, per the request of U.S. troops, Scott and fellow SportsCenter co-anchors hosted a week of programs originating from Kuwait for ESPN’s SportsCenter: Salute the Troops. He hosted a number of ESPN game and reality shows, including Stump the Schwab, Teammates, and Dream Job, and hosted David Blaine’s Drowned Alive special. He hosted a special and only broadcast episode of America’s Funniest Home Videos called AFV: The Sports Edition.  On June 22, 2014, Scott was selected to co-host the first SportsCenter to originate from DC-2 (Digital Center 2) at 11 p.m.

Scott was married to Kimberly Scott from 1993 to 2007. They had two daughters together, Taelor and Sydni. Scott lived in Avon, Connecticut. At the time of his death, Scott was in a relationship with Kristin Spodobalski. During his Jimmy V Award speech, he told his teenage daughters: “Taelor and Sydni, I love you guys more than I will ever be able to express. You two are my heartbeat. I am standing on this stage here tonight because of you.”  On the morning of January 4, 2015, Scott died in his home in Avon, Connecticut of cancer at age 49, 6 months before his 50th birthday.