With the victory, Rise and Shine move in to third position on the log standings.
The hosts got off to a dream start with Bongile Booi profiting from Jabulani Maluleke's through ball to give his side a 1-0 advantage with less than a minute on the clock.
17 minutes later, it was 2-0 with Walter Musona getting on the end of Rodney Ramagalela's cross to double the lead.
But Usuthu equalised in the 28th minute through striker Bonginkosi Ntuli, who grabbed his third in two games. Ntuli tucked home from close range after good work in the build-up by Phumlani Gumede.
However, Musona would collect his brace on the stroke of half-time to restore the two-goal advantage for Rise and Shine.
A fantastic run by Usuthu striker Emiliano Tade then set up Siyethemba Sithebe for the visitors' second as the deficit was cut to just one at 3-2 after 54 minutes.
It was a fairly mild-tempered encounter, with the first booking of the match only coming in the 64th minute when Musona was yellow-carded for a push on Gumede.
Replacement striker Mphambaniso had a chance to extend the hosts' lead with twenty minutes to go but his looping effort went wide of Siyabonga Mbatha's post. But it would not matter as the hosts held on for the precious three points.
AmaZulu: Mbatha, M.Gumede, Mabaliso, P.Gumede, Nyongo, Ncube, Morton, Vilakazi, Sithebe, Tade, Ntuli.
Subs: Muramabadoro, Konqobe, Daroph, Karuru, Ramphela, Ncobeni, Cele.