Mokwena comes highly-rated following his impressive work with the Brazilians over the past two seasons.
Alongside Pitso Mosimane and Manqoba Mngqithi, Mokwena helped the club to the Premiership, Telkom Knockout, Caf Champions League and Caf Super Cup titles during his two-year stay.
He joins the Buccaneers on the recommendation of Milutin 'Micho' Sredojevic, who took over from Kjell Jonevret over a week ago.
"Rhulani's approach to tasks is done in a commitment that is noteworthy. I am pleased that he accepted the challenge," Sredojevic told the Bucs website.
Meanwhile, Mokwena has thanked Sundowns for giving him the opprtunity to grow as a coach.
"I thank the President, Mr Patrice Motsepe and coach Pitso Mosimane for not only providing me with an opportunity; I thank them for the grace with which they accepted and supported my acceptance of the Orlando Pirates challenge," Mokwena said.