The 30-year-old Shanghai Shenhua striker struck five times as the Super Eagles finished third in Egypt, bagging him the top scorer honours with two goals more than Sadio Mane, Riyad Mahrez and Cedric Bakambu.
"It's been an amazing 5 years journey, but after the due consultation and extensive discussion with my family, I have decided it's time for me to retire from the national team," Ighalo said in a statement.
"It's been an eventful and most memorable opportunity to serve my country with pride, passion and contribute my quota to the development of our football.
"It's now time to concentrate on club football and give the younger players a chance to learn and grow."
Ighalo almost quit Nigeria duty after last year's World Cup following sharp criticism and even death threats, but was encouraged to stay on by Gernot Rohr, who Ighalo says stood by him "against all odds".
He repaid in full Rohr's faith in him, finishing top scorer in qualifying for the tournament before his impressive showing in Egypt, which featured a standout display as Nigeria knocked out defending champions Cameroon in the last 16.
Ighalo scored twice and set up Alex Iwobi's winner in a thrilling 3-2 win.
In total Ighalo scored 16 goals for Nigeria in 35 appearances, and he also captained the country's Under-20 team to the 2009 World Cup, also held in Egypt.