The 43-year-old tactician, widely known as Kanu, returns to the dugout after his departure from Chippa United, where his spell ended with three matches remaining in the previous season.
Highbury confirmed the appointment on Friday, signalling their intention to strengthen their push for promotion after narrowly missing out on playoff contention last term.
In a statement announcing the move, the club expressed confidence that Vilakazi's experience and football philosophy make him the right fit to lead their next phase of growth.
"Highbury FC is delighted to announce the appointment of Vusumuzi Vilakazi as the club's new head coach," the club said.
"Following positive and productive discussions, the club has reached an agreement with coach Vilakazi, who will lead the team into the upcoming season.
"Coach Vilakazi brings a wealth of experience, strong leadership, and a clear football philosophy that aligns with the club's ambitions."
Vilakazi arrives with extensive knowledge of South African football, having previously worked with AmaZulu FC, Richards Bay FC and Golden Arrows. He also served as technical director at Chippa before later taking over coaching responsibilities.
For Highbury, the appointment appears aimed at converting promise into a genuine promotion challenge. The club ended last season in sixth position in the Motsepe Foundation Championship, finishing 10 points outside the promotion playoff places.
Vilakazi will now be tasked with turning Highbury into one of the division's serious contenders in the new campaign.