De Zerbi took over the Seagulls midway through the 2022/23 season after the departure of Graham Potter and led the club into the Europa League in his first season after a sixth-place league finish.
"I am very sad to be leaving Brighton, but I am very proud of what my players and staff have achieved with the support of everyone at the club and our amazing fans in the past two historical seasons," De Zerbi said in a club statement.
"We have agreed to end my time at Brighton so that the club and I can continue to work in the way that suits each of us best, following our own ideas and visions, as well as our work and human values.
"I have really enjoyed an intense and challenging two years working in the Premier League, not least competing in four major competitions this season. Leaving now provides me with time to take a break before deciding on my future plans."
Brighton chairman Tony Bloom said: "Roberto has given us two excellent seasons of service in which he has led the club to new heights, not least our first-ever European campaign which will live long in the memory of Albion fans."
"We have mutually agreed to end Roberto's contract at a time that suits both parties allowing us the earliest opportunity to plan for next season, and Roberto plenty of time to consider his next move and his future.
"I am sure our fans will give Roberto and his staff a wonderful and fully deserved send-off at the Amex before, during and after tomorrow's match.
"In the meantime, I'd like to thank Roberto and his staff for all their hard work in the past two seasons. They all leave our club on good terms and with our very best wishes for the future."
Brighton's sixth-place finish under De Zerbi was their highest-ever in the top flight and they ventured into the last 16 of the Europa League this term.
His imminent exit comes amid persistent speculation over his future, having been previously linked to the Liverpool job to replace Jurgen Klopp.
The Reds have since sided with Feyenoord boss Arne Slot but De Zerbi is still courting interest from Bayern Munich, who are set to be in the market for a new manager.
Current boss Thomas Tuchel will leave the German side this summer and confirmed his plans earlier this week.
