Leonardo informed the board of his decision on Wednesday - a week after learning he would be banned for the whole of next season for pushing a referee following a Ligue 1 match in May this year.
He will leave the French champions at the end of August and will depart with the gratitude of Al-Khelaifi for his work at the Parc des Princes, but the Qatari businessman also has his eyes very much on the future.
"I really understand his decision," Al-Khelaifi said in L'Equipe. "I respect it, even if I regret it deeply. Leo has done an excellent job over the past two years to bring a lot of credibility to the sporting aspect of our project.
"I thank him for this work and wish him the best for the future."
He continued: "Seeing executives go is part of the life of a club or any business. People come and they go... The project does not stop.
"PSG now has over 200 employees, including players. The club is growing very fast and there is no-one who can prevent this growth from continuing.
"Nothing can stop us. We continue to build our team and our club, to become a major European competitor in the years to come.
"Today, we are working to recruit new players to add to our great staff of champions. That is my immediate priority."
Leonardo has overseen intense transfer activity in the two years since being appointed in July 2011 in the wake of the Qatar Investment Authority's takeover.
During the 43-year-old's time in Paris, the club signed the likes of Zlatan Ibrahimovic, Marco Verratti, Ezequiel Lavezzi, Lucas Moura, Javier Pastore, Thiago Motta and David Beckham - with the Ligue 1 title duly following last term.
Leonardo was also key to the appointment of Carlo Ancelotti as head coach, although the Italian has since left to take charge of Real Madrid.
His influence over new manager Laurent Blanc was always likely to be diluted by the increased ban he received from the French Football Federation (FFF) for allegedly pushing referee Alexandre Castro following a match against Valenciennes on May 5.
Leonardo was initially handed a nine-month ban but, after a failed appeal, it was increased last week to expire on June 30, 2014, during which time he could not be present on the touchline or enter referees' dressing rooms.