Five-time CAF Champions League winners Zamalek started this season's competition well with a 2-0 win over Douanes Niamey.
Goals from Mohamed Zakaria and Momen Zakaria gave the Egyptian side a comfortable first leg lead in the preliminary round, with the second leg in Nigeria next weekend.
Leopards de Dolisie, who reached the group stages of last season's tournament, did not have such a solid start to their campaign as they were held to a goalless draw by Rayon Sports.
The Congolese side narrowly missed out on a semi-final spot in 2013 but they will need to raise their game in Rwanda if they want to reach the first round this time.
Swaziland's Mbabane Swallows provided a major upset on Sunday as they produced a fantastic performance to beat Nkana 2-0.
The Zambian side were unable to cope with their hosts in the Swazi capital, and the Swallows secured victory thanks to two goals in five second-half minutes from Kudzanayi Matanda and Felix Bardenhost.
There were also good wins for Dedebit, Vita Club, Dynamos and Enyimba on Sunday, with all four sides scoring three goals in their first legs.
Ethiopia's Dedebit beat KMKM 3-0, V Club inflicted a 3-1 win on 10-man Kano Pillars, Enyimba recorded the same scoreline against Anges Notse thanks to two late goals while Dynamos comfortably beat Botswana's Centre Chiefs 3-0.
Ghana's Asante Kotoko were also winners after beating Liberia's Barrack Young Controllers 2-1 in Kumasi, Kwabena Adusei netting two penalties to seal victory for the hosts.
Elsewhere, Berekum Chelsea beat Atlabara 2-0, while Noadhibou against Horoya and Les Astres' game with Akonangui both ended in draws.