Aduana Stars of Ghana look set for a place in the group stage of the Confederation Cup after thrashing Fosa Juniors of Madagascar 6-1 in their play-off first leg on Sunday.
Sunday's other first legs were much tighter affairs with home wins for Sudan's Al Hilal, Ivorians Asec Mimosas and Gor Mahia of Kenya.
Mali's Djoliba were the only side to earn a win away from home as they overcame Nigeria's Mountain of Fire and Miracles (MFM) 1-0.
The second legs are set for April 17 and 18 after which the 16 overall winners will be drawn into four groups.
Aduana Stars were awarded three penalties against visiting Fosa and converted them all with Sam Adams successful twice and Zakaria Mumuni.
Fosa, who are competing in Africa for the first time this year, began well with Jose Randrianantenaina giving them a fourth-minute lead.
Elvis Opoku levelled soon after and the two Adams spot-kicks gave Aduana a 3-1 half-time advantage.
After Mumuni scored his penalty in the second half, Opoku and Bright Adjei completed the rout with goals in the final five minutes.
Al Hilal were the only other team to score more than once on Sunday and will take a 2-0 lead to Nigeria over Akwa United.
Sadiq al Nour and Hussein Ibrahim scored within five minutes midway through the opening half to earn Hilal a 2-0 victory over Akwa United of Nigeria in Omdurman.
Akwa losing completed a miserable day for Nigerian challengers as MFM fell 1-0 at home to Djoliba in Lagos.
Mohammodou Cisse netted after 78 minutes to leave 2012 Confederation Cup runners-up Djoliba needing just a draw in Bamako to reach the mini-league phase.
Rwandan Jacques Tuyisenge converted a 78th-minute penalty to give Gor Mahia a 1-0 home win over 2017 Confederation Cup runners-up SuperSport United of South Africa in Machakos.
Former African champions Asec also won 1-0 at home to Belouizdad of Algeria with the only goal coming from Togolese Komlan Agbegniadan on 50 minutes in Abidjan.
Sunday's Confederation Cup results:
Aduana Stars (Ghana) 6-1 Fosa Juniors (Madagascar)
Al Hilal (Sudan) 2-0 Akwa Utd (Nigeria)
Asec Mimosas (Ivory Coast) 1-0 Belouizdad (Algeria)
Gor Mahia (Kenya) 1-0 SuperSport Utd (South Africa)
MFM (Nigeria) 0-1 Djoliba (Mali)