The eight-time Grand Slam winner and Olympic gold medallist only began coaching Djokovic last season ahead of the French Open, ending 11 years away from the sport.
The 30-year-old Serb has struggled to rediscover his 12-time Grand Slam title-winning form following a lengthy setback with an elbow injury.
Djokovic won just two titles in 2017 and only went as far as the quarter-finals in the year's Grand Slams, having won two and lost in the final of a third the previous year.
"I wish him only the best moving forward," American legend Agassi told BBC Sport.
"With only the best intentions, I tried to help Novak. We far too often found ourselves agreeing to disagree."
The split means that the only coach in Djokovic's team is Czech former world number eight Radek Stepanek, who joined part-time in November 2017.