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Hlatshwayo nodded home a Dillon Sheppard free-kick shortly before half-time, before Pule extended the home side's lead 18 minutes into the second period to all but secure maximum points at Bidvest Stadium.
A fourth win of the current campaign,
Gavin Hunt will be pleased with his side's fourth win of their campaign against bottom-of-the-log AmaZulu who are yet to win this season.
Wits welcomed back goalkeeper Moeneeb Josephs from injury. The shot-stopper made his first appearance of the season after missing all nine of Wits' games so far this season.
The gloveman put in a solid shift and hardly looked like a player nursing himself back to full fitness.
A relieved Hunt watched on as Wits returned to winning ways after a largely frustrating month of September, in which the Johannesburg team suffered a hat-trick of defeats to Orlando Pirates, in both league and MTN8 action.
A quiet opening period saw a tentative start with little in the way of chances for either side.
Wits looked more likely to make something happen but failed to test goalkeeper Tapuwa Kapini.
Wits' persistence, however, paid off as Hlatshwayo skilfully nodded home Sheppard's curling set-piece six minutes before the interval.
Sheppard, a veteran at 35, whipped in a left-footed delivery towards the far post, where an acrobatic Hlatshwayo broke away from his marker to head across the goalmouth and into the opposite corner.
Leading at the break, the Clever Boys went in search of their second but struggled to make an impact in front of goal.
Eventually, after some huff and puff, the Students put away their second, courtesy of Pule's tap-in.
Jabu Shongwe did well inside the area to lose the Usuthu defender, before delivering a ball across the face of goal, which goalkeeper Tapuwa Kapini failed to deal with and let it slip through his fingers.
An advancing Pule met the cross at the back post and slotted home to give the Johannesburg outfit further breathing space with 25 minutes left to play.
In the end, despite a late charge by AmaZulu, Wits ran out worthy winners, in front of an on-looking national coach Shakes Mashaba, who was in attendance and looked pleased to see some of his stars who made it into his latest Bafana Bafana squad.
