After retiring from basketball in 1991, Lowe took a job as an assistant coach with the Minnesota Timberwolves. Halfway through the 1992–93 season he took over as head coach of the struggling Timberwolves and remained in that position until the end of the 1993–94 season. From 1994 to 1999, Lowe served as an assistant coach to Mike Fratello with the Cleveland Cavaliers. Lowe returned to the Timberwolves organization in 1999 for one season as assistant coach.
The 2000–01 NBA season became Lowe's second stint as a head coach when he assumed the role for the Vancouver Grizzlies. He was the fifth head coach in the team's short history and led them to a franchise-best record of 23–59 in his first season and again the following season in 2001-02, when the Grizzlies relocated to Memphis. Sidney Lowe resigned from his coaching duties early in the 2002-03 season after starting 0–8, leaving his head coaching record at 79 wins against 228 losses (.257 winning percentage). In 2003, he returned to Minnesota once again to take an assistant position under then head coach Flip Saunders. Lowe followed Saunders to the Detroit Pistons in 2005 and remained an assistant coach there through the 2006 season.
In his first season at the helm of the NC State program, Lowe became just the third Wolfpack coach, after Everett Case and Press Maravich, to win 20 games and defeat the other three North Carolina institutions in the ACC (Duke, North Carolina and Wake Forest). He is one of only four NC State coaches to have coached in the ACC Championship game in their first year.
In spite of the early success, Lowe failed to lead NC State to the NCAA tournament, and his teams only made two appearances in the NIT. He had an overall winning record (86–78) after five years but only a 25–55 conference record. Lowe resigned as head coach of NC State, accepting a buyout of the last two years of his contract, on March 15, 2011. Later that year, he joined the Utah Jazz as an assistant.
On February 18, 2013, Lowe was arrested for not filing North Carolina income taxes for three straight years. He was released on bond.