Gaines began his stint as Ball's agent after he left UCLA following his freshman season. Ball, 21, was the No. 2 overall pick in the 2017 NBA Draft.
"Harrison Gaines has been a trusted advisor and close friend for many years," Ball told ESPN in a statement. "He guided my NBA career with integrity and always had my best interests at heart."
"Harrison has always had my back and although we will no longer be working together after mutually deciding to part ways; our relationship will always be bigger than basketball."
Sources told Yahoo Sports that Ball's father LaVar Ball has since met with several NBA agents on his son's behalf. League sources told Yahoo that LaVar Ball has "re-emerged as the shot-caller" in orchestrating Lonzo Ball's next move.
The move follows Ball's breakup with Big Baller Brand co-founder Alan Foster. Ball and Foster severed ties two weeks ago. The Lakers guard is now suing Foster for damages of at least $2 million.
"Lonzo Ball was the first client to sign with me," Gaines said in a statement.
"He has been nothing short of phenomenal and is one of the bright young NBA Stars. I thank him and his family for giving me an opportunity. Mutually, we have decided to part ways. I wish Lonzo great success in the future. As I turn this page, I will continue to work hard for all of my clients."
Ball's season ended in March due to a left ankle injury. The 6-foot-6, 190-pound guard averaged 9.9 points, 5.4 assists and 5.3 rebounds in his second season, appearing in 47 games for the Lakers. Ball averaged 10.2 points, 7.2 assists and 6.9 rebounds per game during his rookie campaign.
The Lakers have three games remaining on their regular season schedule, starting with a clash against the Clippers at 10:30 p.m. Friday in Los Angeles.