“We can’t help you if you’re not hungry enough to get out there and compete for the business that is going to be available,” Clinton told a lunchtime crowd gathered at the State Department for a first-of-its-kind global business conference. Noting that American companies are sitting on “large cash reserves,” Clinton called on them to “take informed risks that have always been the key to success.”

Clinton made the appeal at the end of an address outlining how she is refocusing American diplomacy on promoting job creation at home. The approach, which she’s labeled economic statecraft, aims to boost exports, increase foreign investment here and help American companies navigate overseas markets.

“Why, you might ask, is the Secretary of State now spending as much time thinking about market swings as missile silos?” she asked rhetorically. “Well, to put it very plainly, Americans need jobs.”

The two-day confab is pulling together senior administration officials, corporate executives, representatives of American chambers of commerce abroad and diplomats from 120 countries. Clinton said the United States is playing catch-up with other countries that have already moved to put economics at the center of their foreign policy — and that the conference is geared to accelerate it.

In her speech, Clinton announced that the State Department has hired its first-ever chief economist, Heidi Crebo-Rediker, a former investment banker working most recently as a top advisor to the Senate Foreign Relations Committee. And she ticked off other moves that the Obama administration is making to partner with American companies abroad: training diplomats in economics and finance; instructing ambassadors to hold monthly conference calls for American businesses operating locally; lobbying foreign governments on behalf of heavy-hitting contractors like Boeing (BA) and GE (GE); and matching support to American companies whose foreign competitors are getting unfair financing help for their exports.

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Clinton closed with the call for companies to “help us help you.” Clinton said foreign leaders frequently ask her why American businesses aren’t a bigger presence in their countries: “How come they’re not here competing for this construction contract or that mining deal? What are they waiting for?”

It was a point that resonated with the audience. Before Clinton’s speech, Carol O’Brien, executive director of the American Chamber of Commerce in South Africa, told Fortune she and many other African officials had come to deliver the message that the United States needs to develop a plan for investing there. As it is, she said, the Chinese are “raping” the continent, stripping natural resources and sending them home instead of making the kind of sustainable investments that would support economic development. She said Americans, by comparison, are non-existent.

State Department officials, meanwhile, are planning to take the business conference show on the road, hosting another one next month in Japan, with similar events in Latin America, Europe and Africa to follow.