Referring to mass protests in Egypt, Tunisia and other Arab countries, Clinton told a security conference in Germany that the "challenge is to help our (Middle East) partners take systematic steps to usher in a better future."
On Friday US President Barack Obama delivered a clear hint that Egyptian President Hosni Mubarak should step down now and make way for a political transition amid mass protests calling for his ouster and democratic change.
In an update of a warning speech she gave last month in Qatar calling for reform in Arab countries, Clinton said the Middle East was being battered by a "perfect storm of trends."
She spoke of too many young people seeking too few jobs in countries with depleting water and energy resources -- and expressing their frustrations on social-networking sites.
"This generation is rightly demanding that their governments become more effective, more responsive, and more open," the chief US diplomat told leaders and senior officials from Europe, Russia and Afghanistan.
"This is what has driven demonstrators into the streets of Tunis, Cairo, and cities throughout the region. The status quo is simply not sustainable," Clinton said.
"Across the region, there must be clear and real progress toward open, transparent, fair, and accountable systems," she said.
She said changes were occurring at different speeds in different countries, but each must undertake the journey toward democracy.
"There are risks with the transition to democracy," she said, adding it can be chaotic and can cause short-term instability.
"Even worse, the transition can backslide into just another authoritarian regime," she said.
"Revolutions have overthrown dictators in the name of democracy, only to see the political process hijacked by new autocrats who use violence, deception, and rigged elections to stay in power, or to advance an agenda of extremism," she said.
"The transition to democracy will only work if it is deliberate, inclusive, and transparent," Clinton said.