"Across this region the winds of change bring both promise and peril," he said, calling his visit "an opportunity to reaffirm the unbreakable bonds between our nations, to restate America's unwavering commitment to Israel's security, and to speak directly to the people of Israel and to your neighbors."
Seeking to alter a perception among many Israelis that his government has been less supportive of Israel than previous U.S. administrations, Obama declared the U.S.-Israeli alliance "eternal."
"It is forever," he said to applause as Israeli and U.S. flags fluttered in a steady breeze under clear, sunny skies.
Even before leaving the airport for Jerusalem, Obama offered a vivid display of the U.S. commitment to Israeli security by visiting a missile battery that is part of Israel's Iron Dome defense from militant rocket attacks. The United States has invested hundreds of millions of dollars in developing the system with Israel.
Obama and Netanyahu toured the battery, brought to the airport for the occasion. They met and chatted with soldiers who operate the system that Israel credits with intercepting hundreds of rockets during a round of fighting against Gaza militants last November.
"Let me say as clearly as I can: The United States of America stands with the State of Israel because it is in our fundamental national security interest to stand with Israel," Obama said.
"We stand together because peace must come to the Holy Land," he added. "For even as we are clear-eyed about the difficulty, we will never lose sight of the vision of an Israel at peace with its neighbors."
Speaking first at the ceremonial welcome, the nearly 90-year-old Peres offered Obama heartfelt thanks for American defense of Israel.
"A world without America's leadership, without her moral voice, would be a darker world," he said, his voice quivering with emotion. "A world without your friendship would invite aggression against Israel."
Netanyahu, who sparred frequently with Obama over the course of the U.S. president's first term, was equally lavish in his praise.
"Thank you for standing by Israel at this time of historic change in the Middle East," he said. "Thank you for unequivocally affirming Israel's sovereign right to defend itself by itself against any threat."
Although preventing Iran from developing a nuclear weapon is a top priority of both Israel and the United States, Netanyahu and Obama have differed in the past on precisely how to achieve both ends.
Israel repeatedly has threatened to take military action should Iran appear to be on the verge of obtaining a bomb. The U.S. has pushed for more time to allow diplomacy and economic penalties to run their course, though Obama insists military action is an option.
Obama, who joked that he was "getting away from Congress" by visiting Israel, will meet privately Wednesday with both Peres and Netanyahu before visiting several cultural and religious sites aimed at showing his understanding of the deep and ancient connections between the Jewish people and the land that is now Israel.
He will also meet Palestinian Authority President Mahmoud Abbas in the West Bank and travel to Jordan before returning home on Saturday.
But on an itinerary filled more with symbolism than substance, Obama's main focus is on an Israel that is increasingly wary of developments in Syria and Iran. Adding yet another dimension to the trip, Obama landed amid new questions about the Syrian regime's possible use of chemical weapons.
Obama has declared the use, deployment or transfer of the weapons would be a "red line" for possible military intervention by the U.S. in the Syrian conflict. Ahead of Obama's visit, authorities in Israel said they believed that chemical weapons may have been recently used in Syria, although U.S. officials have said they had no evidence to support the Syrian regime's claims that rebels were responsible for a chemical attack.
Even though U.S. officials have set expectations low and previewed no major policy pronouncements, a clear measure of the success of Obama's Israel trip will be how much he is able to reverse negative perceptions.
The centerpiece of the visit will be a speech to Israeli university students on Thursday, during which Obama will again renew U.S. security pledges to Israel as it seeks to counter threats from Iran, protect its people from any spillover in the Syrian civil war and maintain its shaky peace accord with an Egypt that is now controlled by the Muslim Brotherhood.
Obama will make an almost perfunctory visit to the cash-strapped Palestinian Authority's headquarters in the West Bank town of Ramallah, where he will meet the embattled Abbas and assure him that an independent Palestinian state remains a U.S. foreign policy and national security priority.
As Israelis warmly greeted Obama, Palestinians held several small protests in the West Bank and Gaza. Demonstrators in the Hamas-ruled Gaza Strip burned posters of Obama and U.S. flags, accusing the U.S. of being biased toward Israel.
In the West Bank, about 200 activists erected about a dozen tents in an area just outside of Jerusalem to draw attention to Israel's policy of building settlements. The tents were pitched in E1, a strategically located area where Israel has said it plans on building thousands of homes. The U.S. has harshly criticized the plan.
Israeli forces have swiftly dismantled similar encampments built by Palestinians in the past. Abdullah Abu Rahmeh, one of the activists, said Israeli forces surrounded the tent camp but had not moved in.
Despite not coming with any new plan to get the stalled peace process back on track, Obama plans to make clear that his administration intends to keep trying to get talks re-launched.
Obama will close out his Mideast trip with a 24-hour stop in Jordan, an important U.S. ally, where his focus will be on the violence in Syria. More than 450,000 Syrians have fled to Jordan, crowding refugee camps and overwhelming aid organizations.
In his talks with Jordan's King Abdullah, Obama also will try to shore up the country's fledgling attempts to liberalize its government and stave off an Arab Spring-style movement similar to the ones that have taken down leaders elsewhere in the region.
Associated Press writers Mohammed Daraghmeh in Ramallah, West Bank, and Ibrahim Barzak in Gaza City, Gaza Strip, contributed to this report.