Algeria, ranked third in the continent behind the Ivory Coast and Senegal, face resurgent Group B pacesetters Nigeria in Uyo Saturday.
Should 2014 World Cup qualifiers Algeria and Ghana lose, they will trail Nigeria and Egypt by five points in their groups with a third of the six-matchday schedule completed.
Ghana are seeking a fourth consecutive World Cup appearance, which would equal the African record held by Cameroon, and Algeria a third in a row.
While Algeria could not hold an early lead in a surprise 1-1 home draw with Cameroon last month, Nigeria made a perfect start by winning 2-1 in Zambia.
English Premier League pair Alex Iwobi of Arsenal and Kelechi Iheanacho of Manchester City scored the Nigerian goals before the visitors survived a second-half Zambian onslaught.
Nigeria captain John Obi Mikel of Chelsea says a young, hungry 'Super Eagles' squad are desperate to compensate for failing to make the 2017 Africa Cup of Nations finals.
"It is nice to play with young footballers who are hungry and want to establish themselves as first choices," he told the Nigerian media.
"I am reminded of my early days in the national team, playing beside stars like Jay-Jay Okocha and Nwankwo Kanu. It was a great pleasure playing with them.
"It is the same with guys like Alex and Kelechi. We enjoy representing our country, creating scoring opportunities and following the instructions of the coach."
Recently appointed Germany-born coach Gernot Rohr hopes to complete a hat-trick against Algeria after wins over Tanzania in the Cup of Nations and Zambia.
He believes the Africa Cup failure can be turned to the advantage of the five-time World Cup qualifiers.
"Missing out on the 2017 Cup of Nations in Gabon means there is an extra motivation to win our group and go to Russia," he said.
"Everybody knows Algeria have great players, but we also have really good footballers and a family-like atmosphere within the squad."
The Uyo showdown marks the debut of Belgian coach Georges Leekens, the third handler of Algeria this year after Frenchman Christian Gourcoff and Serb Milovan Rajevac.
Gourcoff quit while Rajevac lasted just two matches after players complained about his training methods, team selections and inability to speak French or Arabic.
Ghana coach and former Chelsea manager Avram Grant seems unperturbed by a poor start in Group E last month as bottom seeds Uganda forced a 0-0 away draw.
"We have five matches to go and there is no need for panic," he told reporters. "After losing our opening game at the 2015 Cup of Nations, we went on to reach the final."
Grant welcomes back fit-again Andre 'Dede' Ayew, but injuries sideline fellow midfielder Kwadwo Asamoah and veteran striker Asamoah Gyan.
Egypt pulled off a 2-1 comeback win in Congo Brazzaville and will be fired up to avenge a humiliating 6-1 away thrashing by the Black Stars in a 2014 World Cup play-off.
"I know what Ghana did to us, but that is history," said Argentina-born Egypt coach Hector Cuper. "We fear no team and our target is qualification for Russia."
Morocco coach Herve Renard comes up against a former team when reigning African champions and Group C leaders the Ivory Coast play in Marrakech Saturday.
The Frenchman guided the Ivorians to a long-awaited Cup of Nations title in 2015 and has had a positive impact on sleeping giants Morocco since taking charge last March.
Under-pressure South Africa coach Ephraim 'Shakes' Mashaba knows that anything less than a win against Group D pacesetters Senegal in Polokwane Saturday could see him axed.