Canon found a one-goal first-leg lead insufficient as they lost 2-0 to Etoile of Congo in Brazzaville with Eder Lebaly scoring twice within five minutes during the opening half.
Victory rewarded ambitious Etoile president Rene Oba, who changed coaches despite completing a domestic double last year and hired experienced Romanian Nicolae Burcea.
The Congolese toured west Africa to prepare for the showdown with 1971, 1978 and 1980 champions Canon, who signed two Brazilians in an attempt to become an international force again.
Asante Kotoko of Ghana lost 4-2 on penalties to Ports Authority of Gambia in Banjul after a 1-1 tie on aggregate and the exit of the 1970 and 1983 title holders is likely to trigger the axing of Turkish coach Telat Uzim.
Musa scored after 75 minutes for Ports to cancel the first-leg lead Kotoko took to the heart of west Africa as they sought a second successive appearance in the group phase of the $3.5-million-dollar competition.
The other five former champions in action, Esperance of Tunisia, JS Kabylie of Algeria, TP Mazembe of the Democratic Republic of Congo, Wydad Casablanca of Morocco and Zamalek of Egypt, comfortably cleared the first hurdle.
But there was no shortage of upsets with FC Kallon, a Sierra Leone club owned by Monaco striker Mohamed Kallon, and Niger armed forces side AS FNIS among the surprise qualifiers for the second qualifying round next month.
Albert Foday was the Kallon hero, scoring just after half-time in Freetown to sink fellow debutants Ocean Boys of Nigeria 1-0 following a goalless first leg two weeks ago.
Hamidou Djibo was the toast of AS FNIS as his second-half goals propelled the minnows to a 2-0 victory in Niamey over USMA of Algeria, who lost out on the away-goal rule after building a 3-1 first-leg advantage.
Expensively assembled Mamelodi Sundowns of South Africa moved closer to a third-round showdown with defending champions Al-Ahly of Egypt via a 2-0 away victory over Swaziland police team Royal Leopards.
Strikers Lerato Chabangu and veteran Zimbabwean Peter Ndlovu scored in the second half for Sundowns, who took a 4-2 lead into the return encounter at a baking Somhlolo Stadium near Mbabane.
Draw for the next round
Highlanders (Zimbabwe) v Al Ahly (Egypt)
Desportivo Maputo (Mozambique) v Mamelodi Sundowns (South Africa)
Al Hilal (Sudan) v Zamalek (Egypt)
Nasarawa United (Nigeria) v Port Authority (Gambia)
Fello Star Labe (Guinea) v Etoile Sahel (Tunisia)
APR FC (Rwanda) v Maranatha Fiokpo (Togo)
Al Ittihad (Libya) v AS FNIS (Niger)
St George (Ethiopia) v Etoile du Congo (Congo)
AS Douanes (Senegal) v Wydad Casablanca (Morocco)
FC Kallon (Sierra Leone) v ASEC Abidjan (Ivory Coast)
Young Africans (Tanzania) v Petro Atletico (Angola)
Esperance (Tunisia) v ZANACO (Zambia)
AshantiGold (Ghana) v Royal Armed Forces (Morocco)
AS Adema (Madagascar) v TP Mazembe Englebert (DR Congo)
Mangasport (Gabon) v JS Kabylie (Algeria)
Sewe Sport (Ivory Coast) v Coton Sport (Cameroon)
Teams mentioned first play at home in the first legs on the weekend of 2-4 March. The return legs will be played on the weekend of 16-18 March.