The Buccaneers were keen to revive their hopes of winning this season's PSL title after drawing 0-0 with SuperSport United in Mbombela in midweek.
Milutin 'Micho' Sredojevic made one change to the starting line-up that faced Matsatsantsa with Diamond Thopola replacing Mthokozisi Dube in the right-back position.
Sredojevic's Usuthu counterpart Cavin Johnson included Pirates loanee Thembela Sikhakhane in the starting line-up as the KwaZulu-Natal giants looked to extend their three-match unbeaten run.
Bucs saw most of the ball in the opening stages of the game, but Usuthu took a surprise lead through Mabhuti Khenyeza against the run of play.
The hosts launched a quick counter attack and Ovidy Karuru set-up Khenyeza, who beat Pirates goalkeeper Siyabonga Mpontshane with a tap in to make it 1-0 AmaZulu.
Usuthu continued to set back and launch quick counter attacks with Bucs dominating possession, while searching of an opening in the hosts' defence.
Pirates kept pushing for the equalizing goal and they were awarded a free-kick in a promising area after AmaZulu keeper Siyabonga Mbatha had brought down Thembinkosi Lorch on the edge of the area.
The resultant free-kick was played into the Usuthu box by Luvuyo Memela and Musa Nyatama rose highest to head home to make it 1-1 for Pirates just after half-hour mark.
The goal did not come as a surprise as the Buccaneers have scored 15.2 percent of their goals between 30-45 minutes in the league this season.
The home side nearly restored its lead when Mhlengi Cele's flicked header had Mpontshane scrambling, but the ball eventually went wide of the post and Bucs survived a scare.
The score was 1-1 at the interval between AmaZulu and Pirates following a lively first half.
Micho made a change at the beginning of the second half with Augustine Mulenga replacing Lorch as the Buccaneers looked to take the lead for the first time on the day.
The visitors continued to dominate the match, but they were wasteful and indecisive in the front of goal. Mulenga and his fellow Zambia international Justin Shonga decided to pass the ball instead of shooting inside the Usuthu box.
Mbatha was also having a good game in AmaZulu goal as he produced a fine low save to deny Bucs' top goalscorer Memela as pressure mounted on the hosts' defence.
Bucs finally took the lead in the closing stages of the game when the ball fell kindly for second half substitute Thabo Qalinge, who fired past Mbatha to make it 2-1 to the visitors.
Serbian tactician Sredojevic then made tactical change pulling out offensive minded Memela and he brought in defender-come-midfielder Marshall Munetsi as Bucs looked to contain Usuthu in the dying minutes of the game.
Pirates were able to hold on to their slender lead and ultimately, they secured a 2-1 win over AmaZulu on the day.
The win sees Bucs remain second on the league standings - three points behind the leaders Mamelodi Sundowns, while Usuthu also remained 10th on the table.