The 26-year-old scored in the Nations Cup final with a powerful header, helping his side to beat Egypt 2-1.
Nkoulou has made 74 appearances for the Indomitable Lions and is a former captain of the team.
"After winning the Africa Cup of Nations, I have a sense of having accomplished my duty for country," he told the Foot Mercato website.
"Since the beginning of my career, defending the colours of my country has always guided my steps. This mission has always constituted a motivating factor and one of my priorities.
"This decision has been difficult to take and I considered the advantages and disadvantages before arriving at a conclusion."
However, he hinted he would return to the national team, adding: "A lion never dies."
Africa Cup of Nations-winning Cameroon defender Nicolas Nkoulou is taking a break from international football.