Sadio Diallo brace and strikes by Abdoul Camara, Ibrahima Traore, Mamadou Bah and Naby Soumah secured a one-sided triumph that will give Guinea renewed hope and confidence heading into their final group game with Ghana on Wednesday.
Dipsy Selolwane claimed Botswana's reply from the penalty spot but the Zebras were as good as out of the match by half-time, trailing 4-1 and reduced to 10 men following the dismissal of Patrick Motsepe for a potentially leg-breaking challenge on Pascal Feindouno.
Both these teams lost their opening matches, Botswana beaten 1-0 by Ghana and Guinea losing to Mali by the same scoreline. Botswana striker Jerome Ramathlakwana labelled the match "do-or-die" affair before kick-off, and ultimately it was his side left to face up to almost certain elimination.
Guinea looked dangerous from the first whistle and were ahead after 15 minutes when Camara sent over a dangerous ball from the left wing and Diallo slid in to convert with a clinical finish.
Five minutes later Botswana were level, but only after some penalty-spot shenanigans involving the referee's assistant. First the assistant correctly awarded a penalty against Guinea goalkeeper Naby-Moussa Yattara for his foul on Ramathlakwana.
Yattara made amends by saving superbly from Selolwane's resulting spot-kick only for the assistant to rule he had strayed from his line before making the stop and the referee ordered a re-take.
This time Selolwane tucked the ball away in the opposite corner, much to Yattara's frustration.
Guinea restored their lead after 27 minutes, Camara again the provider from the left for Diallo to slam in his second, while on 42 minutes the impressive Camara deservedly got on the scoresheet when he ran onto a quickly-taken free-kick and slammed the ball in at the keeper's near post.
Just before the interval Motsepe was rightly dismissed for a horrible tackle on Feindouno. The Botswana defender, who had only been on the pitch eight minutes after replacing the injured Ofentse Nato, planted his foot halfway up the shin of his opponent, who was fortunate to escape injury.
Guinea punished Botswana to the full from the resulting free-kick, Traore curling the ball around the wall and in off the post.
Michel Dussuyer's troops continued to make all the running after the break, with Ismael Bangoura firing over after an hour and then seeing his snap shot on the turn brush a post on its way out.
Their pressure eventually told in the 84th minute, Bah seeing his 20-yard drive from the right channel fly into the net with the help of a deflection off a defender, while two minutes later it was six when Bangoura's slide-rule pass found Soumah and the substitute coolly converted.