"Zimbabweans are the ones who can tell Mugabe to leave office through a constitutional means."
'Time to stand up'
Rice made the comments on a trip to Copenhagen, as part of a tour of Europe to say farewell to top diplomats before the Bush administration leaves office in January.
"It is well past time for Robert Mugabe to leave," she said. "I think that is now obvious.
"If this is not evident for the international community, that it is time to stand up for what is right, I don't know what would be.
"The fact is there was a sham election, there has been a sham process of power-sharing talks and now we are seeing not only political and economic total devastation ... but a humanitarian toll of the cholera epidemic."
Rice joined Desmond Tutu, the Nobel laureate and South Africa's archbishop, in the call for Mugabe to step down.
Tutu said on Thursday that if Mugabe did not resign, he should be removed by force and face war crimes charges.
Protesters were rallying in Harare for a new constitution and were joined by angry locals struggling to get money from banks.
|Protests took place in Harare
for a new constitution
Zimbabwe is engulfed in a cholera crisis which has killed at least 575 people and is threatening to spread to neighbouring South Africa and Botswana.
South Africa said on Friday that it was sending a team of military doctors to its northern border with Zimbabwe to treat those infected with cholera.
This has followed an ongoing political crisis since elections in March and a subsequent failure to agree on a power-sharing deal.
Mugabe lost initial presidential elections to opposition leader Morgan Tsvangirai. Tsvangirai pulled out of a second run-off poll in June due to attacks on his supporters which were blamed on Mugabe's allies, handing Mugabe victory.