The Barcelona talisman put Cameroon ahead from a 20th minute set-piece before Angola striker Flavio put his side at level from the penalty spot ten minutes later.
Eto'o regained the lead for the Indomitable Lions six minutes from the interval before completing his hat-trick in the 76th minute.
The win gave Cameroon the summit of their Group B tentatively on three points ahead of the match between Togo and DR Congo.
Eto'o opened the score sheet from a brilliant curling free-kick that went into the top right corner of keeper Joao Ricardo's net.
Angola skipper Akwa was brought down in the area for a penalty kick that was successfully converted by Ahli forward Flavio.
Eto'o restored the lead for Cameroon with a brilliant header after connecting with Rodolph Douala's right wing cross.
Angola pushed forward in search of an equalizer but were stunned when the two-time African Footballer of the Year unleashed a dazzling shot from the edge of the area to put the game out of reach for the World Cup debutants.