Zambia extended their winless streak to seven matches while Morocco crashed to a 3-1 defeat in Tanzania to fall five points adrift of the Ivory Coast in Group C.
Cape Verde Islands, the toast of the recent African Nations Cup with their surprise run to the quarter finals, crashed back to earth with a 4-3 defeat at Equatorial Guinea.
The Democratic Republic of Congo were held to a goalless draw at home by strife-torn Libya on a day the minnows came to the fore.
Zambia were African Nations Cup winners in 2012 and had talked up the prospect of their current generation of experienced players securing a first ever World Cup place in Brazil.
The draw with Lesotho, however, has opened the door to Group D rivals Ghana, who beat Sudan 4-0 in Kumasi.
Zambia still lead the standings by a single point, but have to travel to Ghana at the end of the group phase in September.
Coach Herve Renard said he feared the points dropped to 166th-ranked Lesotho could come back to haunt them.
Lesotho's Litsepe Marabe grabbed a dramatic late equaliser with a rasping long-range shot after Collins Mbesuma had put 10-man Zambia ahead with 17 minutes to play.
Zambia played almost the entire second half down to 10 men after goalkeeper Kennedy Mweene was sent off for a professional foul.
Morocco would need a minor miracle to revive their fortunes in Group C after Tanzania's foreign-based duo of Thomas Ulimwengu and Mbwana Samata (2) scored in a shock win in Dar-es-Salaam.
Morocco had spent the week training for the game in Dubai but could only muster a stoppage-time consolation goal from Youssef Al Arabi.
Their much-vaunted squad has been consistently tipped to succeed on the African stage, but has suffered a series of setbacks over the last 18 months.
Tanzania are second in Group C, one point behind the Ivorians, while Morocco are a distant third with three games left, including a trip to Abidjan.
DR Congo had a chance to join Cameroon at the top of Group I but played out a goalless draw with Libya, whose home-based players have been without league action for two years.
Cape Verde lost their third successive qualifier and are almost certainly out of the running after Equatorial Guinea's Emilio Nsue scored a hat-trick on his debut.
The Mallorca striker only agreed to play for Equatorial Guinea after failing to make Spain's squad for last year's Olympic Games.
Ethiopia went top of Group A with an 88th-minute goal from Getaneh Kebede that gave them a 1-0 home win over Botswana while Mali top Group H after coming from behind to Rwanda 2-1 away.
Egypt host Zimbabwe and Benin visit Algeria on Tuesday.
AFRICAN WORLD CUP QUALIFYING RESULTS
Ethiopia 1-0 Botswana
Equatorial Guinea 4-3 Cape Verde
Tanzania 3-1 Morocco
Lesotho 1-1 Zambia
Ghana 4-0 Sudan
Mozambique 0-0 Guinea
Rwanda 1-2 Mali
DR Congo 0-0 Libya
Liberia 2-0 Uganda