Earlier on, Fagrie Lakay beat his own marker with pace to open the Usuthu defence, but his strike came off the side-netting on three minutes following a pass from Teboho Mokoena.
A quick one-two between Aubrey Modiba and James Keene led to an opening on goal, but the experienced Moeneeb Josephs pulled off a stunning save.
In vain, Keene tried his luck from distance after collecting a loose ball, but his attempt went horribly wide.
Closer to halftime, Josephs pulled off a stunning double save to deny Modiba and Keene in quick succession as the first stanza ended goalless.
Matsatsantsa went ahead early in the second half when Keene beat his marker for pace down the byline to play a low cross for Rusike who finished easily.
Expert goalkeeping from Ronwen Williams denied Usuthu the chance to draw level instantly, as Rusike edged closer to a second but redirected heavily.
Later on, Modiba pulled a stunning shot inches away from goal, with Josephs well beaten as United ran out victors for their first maximum points off the season.