Benin came from behind to stun Nigeria 2-1 and Liverpool star Mohamed Salah scored to salvage a 1-1 draw for Egypt against Guinea-Bissau in World Cup qualifying on Monday.
Ghana were another side to stage a fightback, defeating the Central African Republic 4-3 after trailing at half-time with Crystal Palace forward Jordan Ayew claiming a hat-trick.
Success was particularly sweet for Benin coach Gernot Rohr, the 70-year-old German sacked by Nigeria in 2021 after five years in charge.
The victory lifted Benin, 67 places below Nigeria in the world rankings, to the top of Group C with seven points, two more than Lesotho.
Nigeria, six-time qualifiers for the World Cup and runners-up to hosts the Ivory Coast in the 2024 Africa Cup of Nations, were expected to dominate the six-team section with South Africa.
But after three draws and a loss they lie fifth with just three points. Only Zimbabwe are beneath the Super Eagles.
The defeat by Benin puts pressure on Nigeria coach Finidi George, who took over the reins when Portuguese boss Jose Pereira quit in February after the Cup of Nations.
Former Nigeria star George has won only one of four competitive and friendly matches, and losing to neighbours Benin is sure to trigger criticism.
Benin, disadvantaged by having to play in Ivorian commercial capital Abidjan because they do not have a FIFA-approved stadium, fell behind after 27 minutes.
A long pass was transferred by Samuel Chukwueze to Raphael Onyedika, who bagged his first goal for Nigeria with a fierce shot.
Unperturbed, Benin hit back with goals from Jodel Dossou and captain Steve Mounie before half-time to take a lead they retained till the end.
Dossou burst forward to beat goalkeeper Stanley Nwabali and Mounie celebrated his 50th cap by slamming the ball into the net after a corner was not cleared.
Benin top the table with have seven points, Lesotho have five, Rwanda and South Africa four each, Nigeria three and Zimbabwe two.
Much-changed Algeria win
Lesotho, forced to stage home matches in South Africa as they lack an international-standard stadium, host Rwanda and South Africa play Zimbabwe in Bloemfontein on Tuesday.
Meanwhile, Salah added to his four goals against Djibouti in matchday one by equalising on 70 minutes in Bissau after Mama Balde had put Guinea-Bissau ahead just before half-time.
Salah took the ball across several defenders inside the area before unleashing a shot past goalkeeper Manuel Balde in the top-of-table Group A clash.
Mama Balde had fired past Egypt goalkeeper Mohamed el Shenawy to raise hopes of a home victory in the first World Cup qualifier between the countries.
Guinea-Bissau recently hired former Fulham assistant manager Luis Boa Morte as coach after the failure of Baciro Cande to win a match in four Cup of Nations tournaments cost him his job.
Egypt retained a four-point advantage over Guinea-Bissau with Burkina Faso and Sierra Leone, who drew 2-2 in Bamako, a further point behind.
Ghana led and trailed before building a two-goal lead over the Central African Republic in Kumasi, where Ayew and Louis Mafouta, who plays in the French second tier, scored hat-tricks.
Mafouta completed his treble in the final minute of regular time to create a tense finish before Ghana took over the Group I leadership from Madagascar, who play Mali on Tuesday.
Algeria coach Vladimir Petkovic made five changes after a surprise home loss to Guinea last week and they paid off with a 2-1 Group G victory against Uganda in Kampala.
A careless pass by Mohamed Madani allowed Travis Mutyaba to race through and beat goalkeeper Anthony Mandrea and put Uganda ahead on 10 minutes.
Houssem Aouar levelled in the first minute of the second half and former West Ham United forward Said Benrahma struck the 58th-minute match-winner.
Algeria top the table with nine points, three more than Mozambique, who upset Guinea 1-0 with Geny Catamo converting an added-time penalty.