Atsu set the Black Stars on their way to a comfortable quarter-final victory when he opened the scoring in the fourth minute in Equatorial Guinea's capital, before Kwesi Appiah increased their advantage a minute before the interval.
And Atsu, the winger on loan at Everton from their English Premier League rivals Chelsea, then saw his cross-cum-shot find the net on 61 minutes to take Ghana through to a last-four showdown with the hosts on Thursday.
While Avram Grant's side keep alive their hopes of a first continental crown since 1982, Guinea's Cup of Nations adventure ends without them winning a game at the finals.
Ghana took the lead from their first attack, working the ball into the area from the left before Andre Ayew's backheel allowed Atsu to apply an easy finish. The onus was now on Guinea to try and find a way back into the match, but they created next to nothing, with stand-in captain Ibrahima Traore unable to influence proceedings from the right flank as he had in the group stage.
With half-time approaching, Yattara in the Guinea goal saved from Asamoah Gyan, but Ghana made it 2-0 shortly after with the help of some dreadful defending. Appiah, who was preferred to Jordan Ayew in attack, pounced on a poor clearance by Baissama Sankoh and slotted home under Yattara.
There was a clear gulf in class between the teams and Ghana put any doubts as to the final outcome to bed when Atsu struck again just after the hour mark. Collecting possession wide on the right, he shuffled the ball onto his left foot before whipping what looked to be a cross towards the far post only to see it drop under the bar and into the net.
Guinea's misery was compounded right at the death when goalkeeper Yattara was shown a straight red card for bringing down Gyan on the edge of the penalty box as the Ghana skipper hurtled towards goal.