The Human Rights Council (HRC) has long been accused of bias towards Israel, which is the only country to have a specific agenda item obliging participants to discuss the Jewish state's rights record at every session held.
"It must be said that the HRC's obsession with Israel actually risks undermining the credibility of the entire organisation," Kerry said in his address, which came just hours before Israeli Prime Minister Benjamin Netanyahu was to speak before a powerful pro-Israel lobby group in Washington.
"It has the potential to limit the good that we have to do," Kerry told the opening of the main annual session of the council -- which aims to protect human rights around the globe.
The US administration has opposed Netanyahu's arrival in the US, which will culminate on Tuesday with an address to the US Congress on the Iran nuclear negotiations, saying the visit will undermine the talks as a March 31 deadline for a deal looms.
But Washington remains a staunch defender of Israel -- and has at times been the lone supporter of the Jewish state on the rights council in various resolutions.
Signup to our newsletter and follow us on Facebook and Twitter!
"We will oppose any effort by any group or participant in the UN system to arbitrarily and regularly delegitimize or isolate Israel, not just in the HRC but wherever it occurs," the top US diplomat warned.
He was speaking as a UN report into the Gaza war last July and August, during which some 2,000 Palestinians were killed, was due to be released sometime before March 23.
"When it comes to human rights, no country on earth should be free from scrutiny, but neither should any country be subject to unfair or unfounded bias," Kerry insisted.
He was to meet with his Iranian counterpart Mohammad Javad Zarif in the Swiss lakeside town of Montreux later on Monday.
After years of on-off negotiations, experts say global powers appear to be closing in on a deal that would prevent Tehran from developing a nuclear bomb.
But Israel is worried that Iran and world powers will clinch a deal that eases sanctions on Tehran -- which is what Iran wants -- without applying sufficiently stringent safeguards to prevent it in the future from acquiring the fissile material needed to build a nuclear weapon.