Egypt and Senegal also triumphed to virtually seal places at the 16-nation finals
Morocco became the first qualifiers for the 2017 Africa Cup of Nations in Gabon after beating Cape Verde 2-0 in Marrakech Tuesday.
Star striker Youssef El Arabi scored twice early in the second half, the first from a penalty that resulted in a visiting footballer being red-carded.
Morocco hold a six-point Group F lead over top-ranked African team Cape Verde with two rounds left and a head-to-head advantage having also beaten the islanders last Saturday in Praia.
Frenchman Herve Renard, who led minnows Zambia and underachievers Ivory Coast to the African title in the past three tournaments, replaced Badou Zaki as Morocco coach a month ago.
Egypt and Senegal also triumphed to virtually seal places at the 16-nation finals while Nigeria were eliminated and South Africa look set to join them on the scrapheap.
A second-half goal from Ramadan Sobhy gave Egypt a 1-0 Group G win in Alexandria while Moussa Konate and Papa Souare goals earned Senegal a 2-1 Group K win in Niger.
Record seven-time champions Egypt need one point from a June visit to Tanzania and Senegal one point from games against Burundi and Namibia to be certain of playing in Gabon next year.
But defeat for three-time title-holders Nigeria means they will miss the African football showpiece for the third time in four editions.
Former champions South Africa need a miracle after a drab 0-0 home draw with leaders Cameroon left them five points behind with two matchdays remaining.
Sobhy struck on 65 minutes with a shot from inside the box that was deflected past goalkeeper Daniel Akpeyi.
Victor Moses came close to levelling four minutes from time with a shot that struck the post and trickled across an unguarded goal.
After Konate and Souare had given 2002 runners-up Senegal a two-goal half-time cushion in Niamey, Victorien Adebayor pulled one back for Niger.
Senegal boast a 100 percent record after four rounds and are six points ahead of Burundi, who shocked Namibia 3-1 in Windhoek with Fiston Abdul Razak bagging a brace.
South Africa, whose midfielder Hlompho Kekana scored a wonder goal from inside his half against Cameroon last Saturday, flopped in Durban.
The Indomitable Lions were content to sit back against rivals too slow and predictable to create openings in a match they had to win.
Minnows Mauritania forced a 0-0 draw in Gambia and host Cameroon in a top-of-the-table clash during June knowing victory will give them the lead.
Max-Alain Gradel scored for defending champions Ivory Coast as they drew 1-1 in Sudan to retain a one-pont Group I lead.
Liberia moved two points clear of more fancied Tunisia and Togo in Group A after a 5-0 win over traditional whipping boys Djibouti in Monrovia.
William Jebor scored a hat-trick for the Lone Stars, whose last Cup of Nations appearance was 14 years ago when legend George Weah was captain.
Togo were held 0-0 by Tunisia in Lome despite the return from self-imposed exile of star striker Emmanuel Adebayor.
Democratic Republic of Congo scored late in each half through Joel Kimwaki and Jonathan Bolingi to beat Angola 2-0 In Luanda and build a two-point Group B advantage.
Uganda, whose last played at the finals in 1978, wasted several good chances in a 0-0 Kampala draw with Burkina Faso, who top Group D on head-to-head records.
Ethiopia led Group J pacesetters Algeria three times during a dramatic 3-3 draw in Addis Ababa with Faouzi Ghoulam salvaging a point by converting a late penalty.
Guinea came from behind for a crucial 2-1 win over Malawi in Blantyre with Idrissa Sylla scoring the goal that kept alive hopes of overtaking Group L table-toppers Zimbabwe.