Striker Isaac Success opened the scoring with a cool finish on 10 minutes before Bernard Bulbwa added the second from a counter-attack in the 30th minute.
Success made it 3-0 five minutes to the interval, and on return from the break, he completed a hat-trick from the penalty spot on 61st minute.
The Ghanaians, however, woke up with a brilliant display as captain Boateng Yeboah pulled one back for the Black Starlets. But it was too little, too late.
Nigeria profited from another break in the 69th minute and Success was at his predatory best to finish the move.
The routing was completed in the 90th minute with Iheanacho putting his name on the scorers’ sheet as Nigeria top the group with three points.
The other two teams in the group, Congo and Ivory Coast shared the spoils after playing a 1-1 draw.
Ivory Coast came from behind to equalise in a game the Baby Elephants dominated but could not breakdown a hardworking Congo. The goals came from Ngatsongo Obassi eight minutes into the match and an equaliser from Junior Ahissan. Thereafter the Red Devils of Congo soaked up the pressure and dominance from Ivory Coast to collect a point from Group B.
Nigeria will next face Ivory Coast on Wednesday and win in the game will ensure a ticket to the FIFA U-17 World Cup in United Arab Emirates in October.