The Super Eagles moved up to nine points from three matches in Group B in Africa zone qualifying, while Cameroon remain on two points. Both teams clash again on Monday in Yaounde.
Zambia and Algeria have a point each and meet on Saturday in Lusaka.
After a rather tentative start by the home team, Ighalo marked his return with the opening goal after 29 minutes.
He overpowered his marker after he received a clever assist from skipper Mikel John Obi before he fired past a diving goalkeeper Fabrice Ondoa.
The Eagles doubled their lead in the 43rd minute, when Mikel turned scorer by poking a Victor Moses corner from the left beyond the Cameroon goalkeeper.
In the 55th minute, Moses made it 3-0 when he initiated a quick counter and then released Moses Simon, who did well to pass back to his namesake, who fired the third goal.
A fourth goal from a flying header by substitute Kelechi Iheanacho off an Onazi Ogenyi cross in the 76th minute crowned a very satisfying outing for the hosts.
Both teams went into the attack from the first whistle with Cameroon threatening through Moumi Ngamaleu, but his effort from inside the box missed narrowly as Ikechukwu Ezenwa was the busier of the two goalkeepers in the early minutes of the game.
The Indomitable Lions took the game to Nigeria rather than sit back in their defence.
The Egyptian referee struck off a Nigerian goal by Ighalo for offside after 24 minutes, before Victor Moses header off a Moses Simon cross missed target four minutes later.
However, the home fans celebrated the first goal of this bruising contest just before the half hour with Nigeria never looking back to seal an important win.
Cameroon had their chances. In the 48th minute Ezenwa did well to save a low drive by Zambo Anguissa.
Ezenwa then kept out a tricky shot from distance in the 64th minute before Nigeria again surged forward to create two more goals and complete the demolition of the Indomitable Lions.