Celtic came into the clash with four changes in Jackson Mabokgwane, Tshepo Rikhotso, Teboho Khasipe and Victor Letsoalo to Usuthu's three in Talent Chawapihwa, Michael Morton and Nhlanhla Vilakazi.
Following a slow start, Siphelele Luthuli maintained composure inside the six-yard area to head in off the underside of the crossbar after beating Morton to gift the home side the lead on the half-hour mark.
Usuthu, who came into the match with just five points on the road, drew level four minutes to halftime through top-scorer Bonginkosi Ntuli who found the far corner from a tight angle.
The visitors made a change a moment later in Butholezwe Ncube, who entered in the place of Jabulani Ncobeni as the break dawned.
Usuthu went ahead for the first time in the match when Ncube drifted into the near side of the six-yard area to drill into the bottom corner on 63 minutes.
The vistors were froced into a substitution through injury as veteran full-back Tsepo Masilela replaced Sibusiso Mabiliso, who had struggled with a hamstring.
Celtic pushed to draw level later on in the match, but victory went to Jozef Vukusic's men who end the year in 12th place on the league standings.
Celtic: Mabokgwane, Mashikinya, Ngobeni, Rikhotso, Baloyi, Khasipe, Potsane, Luthuli, Tchilimbou, Letsoalo, Phalane.
Subs: Chaine, Maema, Maloisane, Tani, Nyamende, Ndou, Njoti.
AmaZulu: Boshoff, Darpoh, Booysen, Morton, Mabiliso, Sithebe, Maduna, Vilakazi, Ncobeni, Chawapihwa, Ntuli.
Subs: Josephs, Ncube, Ngubane, M.Gumede, P.Gumede, Magaqa, Masilela.