TP Mazembe of DR Congo defeated Simba of Tanzania 3-1 on Sunday as they embarked on a journey that could lead to a record third consecutive Champions League title.
Patou Kabangu broke the deadlock just 12 minutes into the first half in the second round, first leg game in Lubumbashi.
Cameroonian Narcisse Ekanga added a second midway through the opening half.
Leading scorer Dioko Kaluyituka gave the four-time African champions a three-goal advantage with 64 minutes gone.
However, thousands of Simba supporters who had travelled by bus and car to Lubumbashi finally got something to cheer when Ugandan Emmanuel Okwi pulled one goal back 14 minutes from full-time.
The 2010 Fifa Club World Cup runners-up will travel to Dar-es-Salam for the second leg in two weeks' time.
Club Africain of Tunisia defeated five-time champions Zamalek of Egypt 4-2 in a clash that lived up to pre-match expectations in Rades.
Zimbabwean giants Dynamos secured an important 4-1 victory over Mouloudia Alger in another second round, first leg game on Sunday.
Guthrie Zhokinyi put the home side in the lead on 18 minutes when he converted a penalty.
Dynamos doubled their in first-half stoppage time through a Rodrick Mutuma strike before Denver Mukamba made it 3-0 in the 78th minute.
Farai Vimisai extended the home side's advantage with six minutes remaining but Reda Babouche got a consolation for the visitors through a spot-kick.
The victory gave the former finalists a comfortable cushion ahead the second leg in two weeks' time.
Meanwhile, Asec Mimosas went through to the third round after beating Zimbabwean newcomers Motor Action in a penalty shootout after a goalless draw in Harare.
The match was played over one leg due to the political crisis in Ivory Coast.
Motor Action had the better of the chances in a dull game, but Asec went on to win the shootout 4-2 after misses from Temba Ndhlovu and Masimba Mambare.
"The situation in Ivory Coast is very difficult, so we are very happy with the victory for the supporters in the country," said Asec's French coach Sebastian Desabre.
"It's very difficult to have the qualification decided by just one match, especially as it was decided by penalties."
"This is a young team and we need more work in the coming months."
Asec will meet the winner of the tie between Raja Casablanca of Morocco and Malian club Stade Malien in the third round.
In Ndola, Zesco United of Zambia made full use of home advantage to thump Young Buffaloes of Swaziland 5-0.
A hat-trick from Alfred Luputa and one each from Kangwa Chilehe and Nicholas Zulu carried the day for the Zambian side.
Al Ahly of Egypt beat South African champions SuperSport United 2-0 in their Champions League second round, first leg clash in Cairo on Friday night.
Goals either side of half-time from Osama Hosni and Mauritania-import Dominique Da Silva gave the six-time African champions a comfortable cushion for the second leg.
This was the first match in the competition for the Cairo Red Devils who had a bye in the preliminary round.
They dominated the game from kick-off and could have scored more but for poor finishing.
The second leg will be staged in Pretoria in a fortnight.