Sechaba Mofokeng and Zukisa Ginya scored for Royals before Joseph Malongoane reduced the deficit for Usuthu on the hour mark.
The home side had the early half-chances from setpieces with Sifiso Vilakazi heading over the target in the 4th minute, while Phumlani Mhamha was denied by a good block from the goalkeeper four minutes later.
Then it was the visitors who started to threaten when going forward with Vuyani Nojiya forcing a good low save from Mbongeni Mzimela with a long range effort in the 12th minute.
Then ten minutes later Royals eventually made Usuthu pay for failing to clear their lines as Mofokeng beat Mzimela with a cracking shot from the edge of the box to hand his side a 1-0 lead going into the break.
Craig Rosslee then reacted by making two changes with Njabulo Manqana and Khulegani Madondo coming on straight after the break to replace Nyiko Tshabangu and Sifiso Vilakazi.
However, Usuthu found themselves on the back foot straight after the restart but Mzimela did well to block Thobile Mkhize’s shot at the near post.
Royals did however extend their advantage moments later when Ginya nodded the ball home after the home side had failed to deal with a corner.
The hosts almost struck from a corner at the other end in the 59th minutes, but Namibian international Willem Mwedihanga saw his powerful header cleared off the line.
Usuthu did eventually find the back of the net a minute later as Malongoane collected a pass from Kagiso Senamela and raced past defenders before tucking the ball in off the inside of the post.
The speedy winger was in the thick of things again in the 69th minute, but this time his effort ricocheted off a defender before crashing against the crossbar.
Then in the 76th minute Stanley Kgatla came close to leveling matters for his side after he was set up by Malongoane, but he fired wide of the target.
Royals goalkeeper Gogo made a brilliant save in the 86th minute as he blocked a point-blank header from substitute Makhosonke Bhengu to keep his side in the lead going into the final minutes.
Usuthu did manage to create more opportunities with Malongoane causing problems running in from the right, but Bhengu and Manqana failed to nudge his low cross into an open net in the 90th minute.
The winger had another chance to send the match into extra time in the final minute of added time, but this time he sent his shot crashing against the sidenetting.
AmaZulu: Mzimela, Hlongwa, VHeerden, Mhamha, Mwedihanga, Kgatla, Senamela, Tshabangu, Molangoane, Vilakazi,
Tembu Royals: Gogo, Ginya, Flara, Jojo, Mhlana, Dukada, Nojiya, Mofekeng, Mkize, Gebeda, Spelman
Other Nedbank Cup results:
African Warriors 3-0 Jacksa Spears
Black Leopards 5-4 Cape Town All Stars
Abbas Amidu scored four times for Leopards in the 5-4 extra-time in Polokwane.