He said the vote at the United Nations was about "Israel's future as a Jewish and democratic state, living side by side in peace and security with its neighbours. That's what we are trying to preserve, for our sake and for theirs."
Although he did not mention Israeli Prime Minister Benjamin Netanyahu by name, he addressed head-on the Israeli leader's assertions that the United States had "colluded" and "orchestrated" last week's UN resolution affirming that settlement activity in the West Bank and East Jerusalem have "no legal validity and constitutes a flagrant violation under international law and a major obstacle to the achievement of the two-state solution."
Kerry denied that the United States drafted or promoted the resolution, and took a swipe at the rhetoric coming from Israeli leaders.
"It will be up to the Israeli people to decide whether the unusually heated attacks that Israeli officials have directed toward this administration best serve Israel's national interests and its relationship with an ally that has been steadfast in its support," he said. "Those attacks, alongside allegations of a US-led conspiracy and other manufactured claims, distract and divert attention from what the substance of this vote really was about."
Kerry acknowledged that his vision is not shared and is unlikely to be followed by President-elect Donald Trump.
"President Obama and I know that the incoming administration has signalled that they may take a different path, and even suggested breaking from long-standing US policies on settlements, Jerusalem - and possibly the two-state solution," Kerry said. "That is for them to decide - that's how we work. But we cannot, in good conscience, do nothing, and say nothing, when we see the hope of peace slipping away. This is a time to stand up for what is right."
Trump has said he will move the US Embassy to Jerusalem, a move freighted with political significance in advance of any settlement, and his nominee to be ambassador to Israel, David Friedman, has said Jewish settlements in the West Bank are legal.
About two hours before Kerry started speaking, Trump tweeted his criticism of the Obama administration:
"We cannot continue to let Israel be treated with such total disdain and disrespect. They used to have a great friend in the US, but . . . not anymore. The beginning of the end was the horrible Iran deal, and now this (UN)! Stay strong Israel, January 20th is fast approaching!"
Netanyahu, in turn, promptly tweeted his gratitude: "President-elect Trump, thank you for your warm friendship and your clear-cut support for Israel!"
In a statement released by his office, Netanyahu called Kerry's speech "skewed against Israel."
"For over an hour, Kerry obsessively dealt with settlements and barely touched upon the root of the conflict - Palestinian opposition to a Jewish state in any boundaries," Netanyahu said
Kerry offered six principles that he said would satisfy Israeli security needs and Palestinian aspirations for a homeland.
Most have been proven sticking points in previous negotiations - among them, Jerusalem as a mutual capital for two states; normalised relations with Arab states in the region; and financial compensation for Palestinian refugees, along with acknowledgement of their suffering.