His departure leaves Buonaguidi as the agency's sole creative partner.
Paddy Barnes and Ben Bilboul will continue as its joint managing partners.
Buonaguidi and Ramchandani first met and started as a team at HHCL & Partners in the early 90s. They became the joint creative directors of Chiat Day in 1993 and the co-founders and creative partners of St Luke's in 1995.
Ramchandani said: "I am very proud of the innovative campaigns and free-thinking culture that we have created at Karmarama. I wish Dave and the rest of Karmarama all the best in the future."
Buonaguidi said: "It's sad that Naresh is leaving, though we will carry on working with him on some clients, so there will be some continuity."
Ramchandani's departure follows the news earlier this year that the senior creative team, Vic Polkinghorne and Matt Janes, were leaving the agency for Saatchi & Saatchi.