Malawian outfit Big Bullets were taught a lesson in Omdurman Stadium, with Mudathir Careca scoring twice in a one-sided affair which should see the Sudani Premier League leaders through.
Big Bullets will have to pull off an astonishing fightback in the second leg on April 2 if they are to remain in the competition.
Three-time CAF Confederation Cup winners CS Sfaxien are also in complete control of their first round tie against AC Semassi after coasting to a 5-0 away victory.
The Tunisian side ruthlessly swept aside Sfaxien, who had no answer as the visitors took complete control of the tie.
Mohamed Meftah scored twice as USM Alger consigned AS Pikine to a 5-1 first leg hammering and will be expected to finish off the job in Senegal next month.
Congolese club AC Leopards hold a slender 1-0 advantage after the first leg of their tie at Gor Mahia.
Cesair Ganze scored the only goal of the game to consign the Kenyan champions to defeat, but it is still all to play for ahead of the return leg.
Two-time winners Enyimba were 1-0 winners in their first leg at home to Smouha, while Esperance de Tunis won by the same scoreline at Cosmos de Bafia.
