Rice spoke at the end of her two-day trip to the region, where she met separately with leaders from both sides to pressure them to put aside their disagreements and cooperate on the pullout, which is to begin in less than two months.
"Israel and the Palestinian Authority share a commitment to ensure that disengagement happens smoothly, without violence," she said.
If the withdrawal, which Rice repeatedly called "a historic step," can be completed peacefully, it would build trust that can create the conditions for renewed peace efforts, she said.
CBS News Correspondent Robert Berger reports that Rice believes a peaceful transition could lead to an end to four and a half years of bloodshed.
Rice said the two sides agreed on several issues.
They wanted the houses in the Jewish settlements in Gaza destroyed. They were committed to ensure the flow of goods and people out of Gaza as part of an effort to rebuild an economy that was devastated after more than four years of fighting. They also agreed to discuss what to do with the greenhouses and other commercial assets the Israelis have built in the settlements.
"The United States cannot make the disengagement work, only the Israelis and Palestinians can make the disengagement work," she said.
Israel and Palestinian officials have met in recent weeks to try to ensure that the pullout will not lead to chaos. Israeli Prime Minister Ariel Sharon and Palestinian leader Mahmoud Abbas plan to meet Tuesday to hammer out some of the details.