Substitute Matthew Mbuta from American lower-league club Crystal Palace Baltimore struck the 75th-minute Skopje winner for the 'Indomitable Lions' ahead of a late Match showdown with Senegal in Dakar.
Eto'o, voted African Footaller of the Year a record fourth time two months ago, has scored 27 goals in all competitions for reigning World, European and Italian champions Inter Milan this season.
He constantly troubled a Macedonian defence shaken early on when Tottenham Hotspur defender Sebastien Bassong rattled the woodwork as Cameroon again found Europe a happy hunting ground after a 3-0 win in Poland last year.
Papiss Cisse, the second most prolific scorer in the German Bundesliga this season, opened the scoring midway through the first half as Senegal outclassed Guinea 3-0 in Dakar.
Moussa Sow and Dame Ndoye were on target during the second half for a Teranga Lions team hoping to reach the 2012 Cup of Nations finals after a five-year absence from the African football showpiece.
Morocco and Zambia were other clearcut winners with the Atlas Lions hitting two late goals to complete a 3-0 demolition of Niger while Chipolopolo (Copper Bullets) fared even better by whipping Swaziland 4-0 in Manzini.
Mbark Boussoufa from Belgian club Anderlecht put the Moroccans ahead midway through the opening half in Marrakech, added a second from an 83rd-minute penalty and Mohamed al-Bekkali completed the scoring in stoppage time.
South Africa-based Zambians inflicted severe second-half damage with Collins Mbesuma, Isaac Chansa and Clifford Mulenga bagging goals after James Chamanga had nudged the visitors in front on 15 minutes.
Other matches in southern Africa were affected by weather with a rain-soaked pitch delaying Namibia and Malawi in Windhoek while severe heat forced an early finish to the first half between Mozambique and Botswana in Maputo.
Bernard Harawa scored six minutes from full-time as Malawi triumphed 2-1 while an early second half goal by Almiro 'Miro' Lobo salvaged a 1-1 draw for experimental Mozambique.
Gabon -- co-hosts with Equatorial Guinea of the 2012 Cup of Nations -- overcame a Democratic Republic of Congo side lacking its home-based stars 2-0 in northern French city Rouen via goals from Stephane Nguema and veteran Daniel Cousin.
Tall striker Cicero Semedo took the individual honours with a 17-minute hat-trick as Guinea Bissau came from behind to defeat Gambia 3-1 at Amadora near Portuguese capital Lisbon.
Tanzania defeated Palestine 1-0 in Dar es Salaam, Libya edged Benin 3-2 in Tripoli and Cape Verde Islands shaded Burkina Faso 1-0 in Portugal in other friendlies.