Clinton's pessimistic remarks come as an end-of-year deadline, set by President Barack Obama, looms for the Iranians to prove that their nuclear intentions are peaceful.
She said the administration has offered Iran a chance to participate in meaningful discussions about its nuclear activities and intentions or face fresh penalties for defiance in line with the dual-track, carrot-and-stick approach.
That dual effort, though, has "produced very little," she said, adding that "additional pressure is going to be called for" to get results.
"I don't think anyone can doubt that our outreach has produced very little in terms of any kind of a positive response from the Iranians," Clinton told reporters at a joint State Department news conference with visiting Spanish Foreign Minister Miguel Moratinos.
Clinton's remarks also came as the House prepares to vote Tuesday on legislation that would give the administration authority to punish foreign individuals and companies that sell or ship gasoline to Iran. The bill, known as the Iran Refined Petroleum Sanctions Act, is expected to pass easily.
Similar legislation is under consideration by the Senate but is unlikely to be adopted before January, in part because the administration has asked for some revisions in language. Administration officials also want to see lawmakers deal first with health care reform, according to congressional aides.
"The second track of our dual-track strategy is to bring the international community together, to stand in a united front against the Iranians and try to impress upon them the importance of changing their actions and decisions concerning their nuclear program," Clinton said. "Certainly, additional pressure is going to be called for in order to do that."
As Obama's deadline nears, the administration is also preparing to press the United Nations, individual countries and blocs of nations, such as the European Union, to adopt a range of new sanctions on Iran early next year. Iran is already under three sets of penalties from the U.N. Security Council as well as unilateral sanctions from numerous states.
The administration's suggested package of sanctions includes travel restrictions and asset freezes on specific Iranian individuals and entities along with measures that would target the trade and commerce, insurance and reinsurance, banking, energy and shipping sectors, according to officials familiar with it.
The push toward new sanctions has picked up steam in recent weeks as Iran has bolstered its defiance of attempts to get it to prove its nuclear program is civilian, as it claims, and not a covert attempt to develop atomic weapons as the U.S. and its allies believe.
After agreeing in principle to a scheme under which it would ship uranium abroad to be enriched for a medical research reactors, Iran is now balking and officials have announced plans to build an additional 10 to 20 enrichment facilities. Those actions occurred after the disclosure in September of the construction of a previously secret facility near the city of Qom.
Clinton noted each of these developments in her comments on Monday and said they "should raise deep concern among all people."