"Israel has been tolerating this intolerable situation for nearly a year. Well, I've come here today to say enough is enough," Netanyahu told the UN General Assembly, referring to escalating violence between Lebanese Hezbollah and Israel.
Several delegations walked out as Netanyahu approached the lectern while supporters in the gallery cheered.
"My country is at war, fighting for its life," he said.
"We must defend ourselves against these savage murderers. Our enemies seek not only to destroy us, they seek to destroy our common civilisation and return all of us to a dark age of tyranny and terror," he said.
In southern Lebanon, Israel continued to strike Hezbollah targets while diplomats at the UN voiced fears the attacks could flare into an all-out regional war.
Netanyahu on Friday sought to pin blame for the conflict on Israel's arch-foe Iran, whose delegation was absent for the speech.
He said Israel was defending itself against Iran on seven fronts, including against Hamas in the Gaza Strip.
"There is no place in Iran that the long arm of Israel cannot reach. And that's true of the entire Middle East. Far from being lambs led to the slaughter, Israel soldiers have fought back with incredible courage," Netanyahu said.
"I have another message for this assembly and for the world outside this hall: we are winning," he said.
Israel will press on with discussions on ceasefire proposals for Lebanon in the days ahead, Netanyahu said earlier on Friday, and the United States government warned that further escalation would make it harder for civilians on both sides to return home.
But Netanyahu insisted that Israel's campaign would continue.
"We'll continue degrading Hezbollah until all our objectives are made," he told the UN assembly.
The Israeli prime minister also called for tougher action on Iran's nuclear program, including a return of UN sanctions which were lifted in 2015 under a nuclear deal with major world powers.
"I call on the Security Council to snap back UN Security Council sanctions against Iran because we must all do everything in our power to ensure that Iran never gets nuclear weapons," Netanyahu said.
A Security Council resolution, which enshrined the nuclear deal and provided the power to restore UN sanctions, expires in October 2025.
Netanyahu also reiterated his earlier vows that Israel would block Iran from obtaining a nuclear weapon.
"Iran now seeks to weaponise its nuclear program for the sake of the peace and security of all your countries, and I assure you, Israel will do everything in its power to make sure it doesn't happen."
On the conflict in Gaza, Netanyahu said the war can end if Hamas militants who carried out an October 7 attack in Israel surrender, lay down their weapons and return hostages seized in the attack.
"We'll fight until we achieve victory, total victory, there is no substitute for it," he said.
During the speech, he cited the presence of families of hostages seized by Hamas on October 7.
The war began when Hamas gunmen stormed Israeli communities, killing about 1200 people and taking about 250 hostages back to Gaza, according to Israeli tallies.
Since then, Israel's military has leveled swaths of the besieged Palestinian enclave, driving nearly all of its 2.3 million people from their homes, giving rise to deadly hunger and disease and killing more than 41,000 people, according to Palestinian health authorities.
Senior Hamas official Sami Abu Zuhri condemned the speech.
"Netanyahu's speech is full of lies and contradictions, and the withdrawal of many delegations from the hall is a message that Netanyahu's lies are no longer believed by anyone," Abu Zuhri told Reuters.
"Netanyahu's call for Hamas to surrender is nonsense; surrender is not in the movement's vocabulary, and the problem lies in the existence of the occupation, not with those who are defending themselves," Abu Zuhri said.
The two General Assembly speakers before Netanyahu thumped the lectern as they spoke.
Slovenia's Prime Minister Robert Golob demanded: "Mr. Netanyahu, stop this war now."
Pakistan's Prime Minister Shehbaz Sharif said: "We must act now and demand an immediate end to this bloodshed."
