Cassell was selected 24th overall by the Houston Rockets in the 1993 NBA Draft out of Florida State University. He helped them to two championships in 1994 and 1995. After the 1995-96 season, he was traded to the Phoenix Suns, but his tenure there was brief.

He was soon traded again, along with Michael Finley, A.C. Green and a draft pick to the Dallas Mavericks for Jason Kidd, Tony Dumas, and Loren Meyer on December 26 1996. The next year, he was traded along with Chris Gatling, Jim Jackson, George McCloud and Eric Montross to the New Jersey Nets for Shawn Bradley, Ed O'Bannon, Robert Pack and Khalid Reeves.

Two years later, he was dealt in a three-way trade, which sent him to the Milwaukee Bucks along with Brian Evans, Chris Gatling, and two future draft choices. On June 27, 2003, the Bucks traded him and Ervin Johnson to the Minnesota Timberwolves for Joe Smith and Anthony Peeler. On August 12, 2005, the Timberwolves traded Cassell and a draft pick to the Clippers for Marko Jaric and Lionel Chalmers.

Cassell appears to have found a home with the Los Angeles Clippers; the NBA veteran led them into the Western Conference Semi-finals in the 2006 playoffs with home court advantage in the first round. They beat Denver in five games but would eventually fall to the Phoenix Suns in 7.

Cassell is known for his feistiness and outgoing personality. He was one of the Milwaukee Bucks' "big three" alongside Ray Allen and Glenn Robinson that reached the Eastern Conference Finals in 2001. In Minnesota, he was an integral part of the Timberwolves. He and his teammates were led by 2003-04 MVP Kevin Garnett to the 2004 Western Conference Finals for the first time in franchise history.