"If Kim Jong-un decides to launch a missile, whether it's across the Sea of Japan or some other direction, he will be choosing willfully to ignore the entire international community," Kerry said in Seoul, South Korea.
"And it will be a provocation and unwanted act that will raise people's temperatures."
Kerry, speaking on the first day of four days of talks in East Asia, also said that any missile launch would be a "huge mistake" by North Korea.
"It will further isolate his country and further isolate his people who are desperate for food and not missile launches," he warned.
"They are desperate for opportunity and not for a leader to flex his muscles."
But Kerry played down a new US intelligence report that suggested North Korea had made significant progress in its nuclear weapons programme.
US officials believe North Korea's mid-range missile has a range of up to 2,500 miles - enough to reach the US territory of Guam.
Tensions rose sharply on the Korean Peninsula in December after North Korea tested a Taepodong 2 missile and again in February when it carried out its third nuclear test.
The UN hit back with sanctions, and the start of joint military drills between South Korea and the US last month further irritated the North, which threatened to carry out a nuclear attack on the US mainland.
"We will defend our allies," Kerry said. "We will stand with South Korea and Japan against these threats. And we will defend ourselves."
US President Barack Obama earlier called on North Korea to "lower temperatures", saying no one had an interest in conflict on the Korean Peninsula.