By missing out on the victory, Ghana wholly failed to capitalise on Uganda's shock 1-0 victory over Egypt on Thursday and remain in third on two points, five behind the Cranes in top spot.
The result becomes Cameroon's heaviest defeat in 49 years and leaves their World Cup dreams on the brink of ending.
Ghana, who have been to the last three World Cups, are way off the pace in Group E after being held at home by Congo.
The Eagles are now unbeaten in 33 World Cup qualifying games. There is only honour to defend, there is no importance to this [match]. "If the players have the same attitude I have, we will fight to beat Nigeria on Monday", he vowed.
"The win on Friday was just the first of the two clashes, I hope we get to Cameroon and finish the job there on Monday. I don't think this is possible".
Obi Mikel's clever punt from midfield set Ighalo away for the first goal in the 29th minute.
Second half goals from Victor Moses and Kelechi Iheanacho saw the Super Eagles securing their biggest win ever over Cameroon.
Perhaps, substitute Iheanacho failed to read the script that the Eagles were playing the African champions, and made a decision to head the fourth from a sublime Ogenyi Onazi pull -out with 13 minutes left.
The Chelsea wing forward drew out the Indomitable Lions central defenders before putting on Shehu Abdullahi who cut back for a running Moses to score with a composed finish.
Nigeria's dominance continued in the second half, with Moses ending a blistering counterattack with a goal in the 54th minute.