The Clever Boys had the upper hand in the first half but had to wait until five minutes before the break for Ben Motshwari to score the opening goal.
Another goal early in the second half put the home side in a comfortable position as Sthembiso Ngcobo headed home Tebogo Moerane's pinpoint cross.
Ngcobo completed his brace a few minutes later to take the score to 3-0, while Vincent Pule missed a great chance to add to their advantage.
Gavin Hunt's side travel to Swaziland for the second leg at Lobamba Stadiumon February 28 and will be confident of seeing it through.
The winners will face either Volcan Club (Comoros) or Petro de Luanda (Angola) in the next round.
Wits XI: B Pule, Kwakman, Ntshangase (c), Lecki, Moerane, V Pule, Doutie, Zuke, Motshwari, Ngcobo, Katongo
Subs: Josephs, Nergadze, Mosiathlaga, Setelele, Paseka, Kebede, Jappie
Royal Leopards: Mp Dlamini, Fakudze, Ntimane, Ntshalitshali, Ma Dlamini, Nkambule, Nxumalo, Malambe, Lukhele, Steenkamp, Ju Gama
Subs: Nc Dlamini, Mu Dlamini, Thwala, Mkhontfo, Khumal, Mavimbela, Jo Gama