"Our goal is clear: a comprehensive peace, including two states living side by side in peace and security, a Jewish state of Israel, with true security for all Israelis, and a viable, independent Palestinian state with contiguous territory that ends the occupation that began in 1967 and realises the potential of the Palestinian people," Rice said.
"We all must decide whether we are serious about peace or whether we will lend it only lip service."
In her speech Rice also urged an end to what she called "anti-Israel vitriol" at the United Nations, where the General Assembly is expected to debate the Goldstone report on war crimes carried out during Israel's war on Gaza earlier this year.
The report concluded that both Israel and the Palestinian territory's Hamas rulers, committed war crimes and possible crimes against humanity, although it is more critical of Israeli troops for "terrorising and targeting" civilians.
"Member states must once and for all replace anti-Israeli vitriol with recognition of Israel's legitimacy and right to exist in peace and security," Rice said, making no specific mention of the Goldstone report.
The US has previously criticised the report, calling it one-sided.
In a separate meeting with Rice, Binyamin Netanyahu, Israel's prime minister, hailed the US position on the Goldstone report, a statement from his office said.
"The prime minister thanked Rice for the Obama administration's vigorous opposition to the Goldstone report and its ongoing support (of Israel) at the United Nations," the statement said.
On Tuesday, during a meeting with Peres, the Israeli president reportedly told Rice the Goldstone report was an outrage.
According to reports in Israeli media he said the report, compiled by South African jurist Richard Goldstone, had turned the UN into a stage for anti-Israeli lies and baseless stories.
In her conference speech, Rice appeared to reach out to Israeli critics of the US administration's Middle East agenda, saying that Washington remained "fully and firmly committed to the peace and security" of Israel, and committed to fighting extremism.
"We will stand by our friends on the frontlines and we will uphold the inalienable right to self-defence," she said.
Since taking power in January, Barack Obama, the US president, has attempted to restart peace talks.
But his moves to reach out of the Muslim world have alarmed critics in Israel who fear he will depart the near-unconditional support for Israel shown by his predecessors.
The last round of peace talks broke down late last year with no breakthroughs on the main issues dividing the two sides: final borders, the status of disputed Jerusalem and a solution for Palestinians who lost their homes and other property in Israel after it achieved statehood in 1948.
The issue of Israeli settlement construction on Palestinian land remains another key issue.
Mahmoud Abbas, the Palestinian president, has demanded that Israel freeze all settlement construction on war-captured lands and agree to a clear agenda for peace talks before talks can resume.
But Netanyahu has said some settlement construction must continue to accommodate growth of existing settler populations.