Portugal dominated the early stages and opened the scoring just after the half hour mark through FC Porto's Raul Meireles. Eto'o protested the goal to the referee and, having already been booked for a foul on Portugal defender Duda, the Cameroon star was shown a second yellow and then a red card in the 33rd minute.
Portugal took advantage of their numerical superiority and the on-form Meireles grabbed his second of the game in the 46th minute.
Eto'o was making his first appearance for Cameroon since helping his Italian club to an historic treble of the Serie A title, Italian Cup and UEFA Champions League.
However even in his absence the Indomitable Lions, who will play Denmark, Japan and the Netherlands in Group E of the 2010 FIFA World Cup South Africa™, fought back valiantly and reduced arrears in the 69th minute when Webo rose to meet a superb cross into the area and fired a bullet header
Real Madrid striker Cristiano Ronaldo has struggled to make an impact for his national side in recent months and that streak continued, with Manchester United's Nani providing the hosts' third goal nine minutes from time.
Cameroon will play one more friendly, against Serbia on 5 June in Belgrade, before flying to South Africa. Portugal fly out to South Africa later this week and open their tournament against the Ivorians on 15 June, with further Group G matches against Brazil and Korea DPR.