Veteran striker Eto'o called time on an 18-year international career last month but coach Volker Finke - retained in his post despite a shambolic FIFA World Cup campaign in Brazil - oversaw an assured start to the new era.
Lyon forward Clinton N'jie went some way to filling Eto'o's sizeable shoes by opening the scoring on the stroke of half-time and Porto's Vincent Aboubakar sealed the points in the 82nd minute.
DR Congo's efforts were somewhat hampered by captain Youssouf Mulumbu sustaining a hamstring injury midway through the first-half.
Cameroon's fellow Group D heavyweights Ivory Coast secured a 2-1 comeback win against Sierra Leone in Abidjan.
Kei Kamara benefitted from some generous defending to finish from close range and hand the visitors a late first-half advantage
However, Seydou Doumbia made an instant impact, coming off the bench to level matters from Serge Aurier's 63rd-minute cross, before Gervinho drilled home a low winner five minutes later.
The shock result of the day came in Group A as Nigeria continued a turbulent period on and off the field with a 3-2 loss at home to Congo.
The visitors, only in this stage of the competition due to Rwanda fielding an ineligible player during their defeat in the previous round, fell behind to an Efe Ambrose header but Prince Oniangue soon restored parity.
Thievy Bifouma finished off a splendid team move in the 40th minute and the same player netted a second-half penalty after being fouled by Ogenyi Onazi to give Congo breathing space.
Nigeria substitute Gbolahan Salami scrambled home to set up a grandstand finish but Congo held out for a famous triumph.
South Africa are up next for Nigeria, providing the latter's Football Association can avert a global ban by agreeing to FIFA's terms over an ongoing governance dispute regarding political interference.
Algeria built on their impressive World Cup showing with a 2-1 win in Ethiopia - Frenchman Christian Gourcuff's first competitive game at the helm.
Hillel Soudani and Yacine Brahimi were on target either side of half-time before Saladin Said netted a consolation penalty in stoppage time for the home team, whose own coach Mariano Barreto also oversaw a maiden competitive outing.
Elsewhere in Group B, torrential rain and a waterlogged pitch led to the match between Mali and Malawi being postponed. The two teams will try again on Sunday in Bamako.
Ghana struggled to shake off their World Cup malaise in a 1-1 Group E draw with Uganda.
Asamoah Gyan was twice denied by Denis Onyango before Tony Mawejje struck from the edge of the area to give Uganda a half-time advantage.
Andre Ayew levelled matters five minutes after the restart after Abdul Majeed Waris was fouled in the box, but Ghana could not force a win.
There was late drama in the day's final game as Yassine Chikhaoui scored a 90th-minute penalty for Tunisia to snatch a 2-1 home win over Botswana.
Despite being on the back foot for long periods, Botswana clinically stung their opponents on the counter attack through a Joel Mogorosi goal in the 44th minute.
Wahbi Khazri scored a free-kick with 16 minutes to play before Ofentse Nato's handball presented Chikhaoui with the chance to be his nation's hero.
Gabon and Burkina Faso secured home wins in Group C, 1-0 and 2-0 over Angola and Lesotho respectively.
Cape Verde were the day's winners in Group F - Garry, Odair Fortes and Ze Luis responsible for them racing into a 3-0 lead inside 24 minutes against Niger, who could only reply through seasoned striker Moussa Maazou.
The group's other game between southern African rivals Zambia and Mozambique ended goalless.
