The record seven-time African champions face surprise Group F leaders Libya at home and away and need at least four points to take over first place ahead of the final two 2022 World Cup qualifying rounds during November.
Mohamed Salah, fresh from scoring a brilliant goal for Liverpool against Manchester City, switches his attention to 2022 World Cup qualifying this week as Egypt hope to get their campaign back on track.
The record seven-time African champions face surprise Group F leaders Libya at home and away and need at least four points to take over first place ahead of the final two rounds during November.
Only the 10 group winners advance to the final qualifying round and Egypt and fellow first seeds Cameroon, Ghana, Morocco and the Democratic Republic of Congo have catching-up to do.
Here is a look at the situation in each group with 41 matchday two, three and four qualifiers scheduled for seven days from Wednesday.
Riyad Mahrez-captained reigning African champions Algeria have an impressive home record against Niger in World Cup qualifying, scoring 10 unanswered goals in two matches.
Another convincing home win is on the cards for a team boasting an African record 29-match unbeaten run, but second-place Burkina Faso are likely to remain level on points with Algeria by defeating Djibouti.
Table-toppers Tunisia have won all four previous World Cup qualifiers against Mauritania and there is nothing to suggest they will not extend that perfect record in Rades.
A Tunisian side captained by Saint-Etienne's Wahbi Khazri and coached by Mondher Kebaier enter the match boosted by two impressive victories while the Mauritanians have disappointed when losing twice.
It is difficult to imagine any result in Lagos other than a comfortable victory for leaders Nigeria over the Central African Republic, who will lack unavailable Atletico Madrid midfielder Godfrey Kondogbia.
After a routine home win over Liberia last month, a severely weakened Super Eagles side triumphed away to Cape Verde and they will be back to near full strength for the visit of the Wild Beasts.
Considered the toughest section to win as rivals Cameroon and the Ivory Coast have qualified for the World Cup 10 times between them.
The Ivorians hold a one-point lead thanks to a 2-1 home win over the Cameroonians, but the poor state of the pitch at the recently opened national stadium in Abidjan means they must host Malawi in Benin.
Mali have made a good start in the only section that does not contain a previous World Cup qualifier, building a two-point advantage over Kenya and Uganda with Rwanda last.
A Malian squad including Southampton midfielder Moussa Djenepo are handicapped by having to play home matches in Morocco due to the poor state of their stadiums, but they are favoured to beat Kenya.
Libya stole a march on Egypt by snatching a late home victory over Pierre-Emerick Aubameyang's Gabon and then winning in Angola.
After shading Angola, Egypt were lucky to hold Gabon and the draw cost coach Hossam el Badry his job with former Real Madrid manager and Manchester United assistant manager Carlos Queiroz taking over.
Pacesetters South Africa face bogey team Ethiopia, who took four points off them in 2014 qualifiers, leading to Bafana Bafana (The Boys) coaches Pitso Mosimane and Gordon Igesund being sacked.
Ghana and Zimbabwe will have new coaches for back-to-back meetings with Serb Milovan Rajevac replacing Charles Akonnor at the Black Stars and Norman Mapeza succeeding Croat Zdravko Logarusic at the Warriors.
Sadio Mane's Senegal could seal first place with two victories over closest challengers Namibia, another country affected by stadium standards and forced to host matches in neighbouring South Africa.
The biggest threat to the Senegalese will probably come from Peter Shalulile, a consistent scorer for Mamelodi Sundowns, the dominant club in South Africa.
Morocco, whose first choice line-up includes star Sevilla forward Youssef en-Nesyri, will play 'away' matches against Guinea-Bissau and Guinea at home, giving them a huge advantage.
Leaders Guinea-Bissau do not have an international-standard stadium while FIFA currently considers Guinea an unsafe destination after a coup forced Morocco to flee Conakry last month.
Tanzania were seeded fourth, but lead Benin on goals scored with section favourites DR Congo third and without a win despite two goals from recalled 35-year-old Dieumerci Mbokani.
The top two meet in Dar es Salaam and Cotonou and former Aston Villa forward Mbwana Samatta captains a Tanzanian team coached by Dane Kim Poulsen.