This news comes just a day after Abram Mongoya confirmed his resignation just six games into the new Motsepe Foundation Championship season.
Nyatama has reportedly penned a two-year contract, and he joins Upington after a short spell as head coach of Chippa United, having initially arrived at the club as an assistant coach to Sinethemba Badela.
Mongoya was the subject to an internal disciplinary process after his reported "gross misconduct" for taking up a role with the Lesotho national team without approval from Upington.
Nyatama's previous coaching experience includes a spell as caretaker coach for Moroka Swallows.
He was previously linked with Upington City and now takes over the team in sixth place on the league standings with three wins, one draw and two losses.
A club statement read: "Upington City FC is proud to welcome Musa Nyatama as our new Head Coach!
"A leader with experience, passion, and vision — ready to guide The Citizens into a new chapter.
"Let's give Coach Nyatama a warm welcome, Citizens!"
The Nedbank Cup Round of 16 delivered high drama as TS Galaxy stunned Mamelodi Sundowns with a clinical 2-0 win, while Durban City held their nerve to knock out Upington City on penalties after a gruelling stalemate.
Former Kaizer Chiefs midfielder Kgaogelo Sekgota is embracing a new chapter in his life and career after completing a four-month rehabilitation programme at the Hope of Achievers Rehabilitation Centre outside Polokwane.
Musa Nyatama says he sees plenty of potential in the Upington City squad after overseeing a 2-1 win over the University of Pretoria in his first game in charge of the club.
Abram Mongoya has resigned from Upington City after just six games into the new Motsepe Foundation Championship season.
