The Pharaohs were not the only African giants to suffer as neighbours and 2010 FIFA World Cup™ finalists Algeria also lost, along with Nigeria and Togo, while South Africa and Ghana could only manage draws.
But in a result that is unlikely to be easily forgotten, Amadou Kader grabbed the only goal after 34 minutes to help the world number 154 team beat ninth-ranked Egypt in Niamey. It was a second consecutive poor result for Hassan Shehata's men, who drew their opening match of Group G at home to Sierra Leone.
Although only two games have been concluded thus far, the seven-times champions now have just a single point to show for their efforts and face the real possibility of missing out on a place in the finals for the first time since 1982.
Elsewhere in the pool, 2010 FIFA World Cup hosts South Africa could only manage a goalless draw in Freetown, a result that keeps them top of the section with four points, with Niger in second on three and Sierra Leone third on two.
In Group D, late strikes from Eude Dagoulou (81) and Momi Hilaire (86) stole all the points for the Central African Republic against the Algerians. The Desert Foxes, who parted company with their coach Rabah Saadane after only managing a draw in their opening game, looked destined for a point in Bangui until the drama at the death which has now left them rooted to the foot of the table.
Tunisia salvaged some north African pride, though, after managing to secure a 2-1 win over Togo in Group K. Issam Jemaa (38) gave the visitors the lead in Lome, before Sapol Mani (40) made sure the home side went into the break level at 1-1. But Amine Chermiti (83) had the final say with the three points lifting the Carthage Eagles into second, three points behind Botswana.
One of the most talked-about games this weekend was Nigeria's trip to Conakry to face Guinea, a match that was temporarily suspended and then back on after FIFA had banned Nigeria from all competition following government interference in the sport. But the Group B clash did eventually go ahead with Kevin Constant's fifth-minute strike proving the difference between the two sides as the hosts ran out 1-0 winners to move three points clear. In the other match in the pool, Madagascar were 1-0 losers at home to Ethiopia in Antananarivo.
Meanwhile, Zimbabwe missed a good chance to move top of Group A after they could only manage a goalless draw against the Cape Verde Islands in Harare. Libya moved top of Group C thanks to Ahmed Saad (36), who helped them secure a narrow 1-0 win over Zambia in Tripoli.
Finally in Group I, Ghana, Africa's best performers at the FIFA World Cup, played out a lacklustre 0-0 draw at home to Sudan in Kumasi. To compound matters for the Black Stars, star striker Asamoah Gyan was sent off 10 minutes from time, but they held on.
Congo took full advantage of that slip by winning 3-1 against Swaziland. Barel Mouko opened the scoring from the spot after 20 minutes and Francky Sembolo (34 and 73) hit a brace. Darren Christie (36) netted what turned out to be a consolation in Brazzaville.