"It's important now that we talk about why, in tough times, these budget choices are still very, very wise choices for the taxpayer to make," Gates told Reuters in an interview.
The Microsoft co-founder, whose $34 billion foundation is devoted largely to funding health projects in developing countries, said Republican calls to narrow the yawning U.S. budget deficit by slashing overseas aid could weaken the U.S position.
"Any government program should be looked at because the size of the deficit is gigantic and unsustainable," Gates said, noting that the overall U.S. aid budget of about $35 billion is dwarfed by the Pentagon's $700 billion funding request.
"If you look at our defense budget, which as a percentage of GDP or in absolute, clearly it sounds like we want to engage the world," he said. "And yet if your balance is totally guns and aircraft carriers, the general reception you get over time isn't as good."
Gates, one of the wealthiest people in the world, spoke amid a gathering debate in Washington over the future of U.S. aid programs, which some Republicans in Congress have targeted for cuts as the country grapples with its budget deficit.
In a speech to the U.S. Global Leadership Coalition on Wednesday, Gates said U.S. aid policy had a raft of benefits for the country, ranging from stabilizing poor countries before they become security risks to building new markets for U.S. exports as developing countries grow.
"Any claim that foreign assistance to the poorest countries is just money down a rat hole simply doesn't stand up to scrutiny," Gates said, pointing to the eradication of smallpox, decreasing infant mortality and advances in agricultural productivity as key milestones.
Secretary of State Hillary Clinton, who has stressed that development must be as important as defense and diplomacy to U.S. policy, said on Wednesday there was a "great push" in Congress to cut overseas aid spending, requiring everyone to preemptively tighten their belts.
"We have scrubbed our budget for every dollar of savings and we have made very hard choices," Clinton told a gathering of U.S. ambassadors in Washington.
Gates said aid spending was among the best things that government can do.
"I think well-spent aid is uniquely effective among all the different kinds of spending our government does," he said in his speech, adding that foreign aid advances U.S. goals and values for a relatively low cost.
"Right now, the tough choice is to maintain foreign assistance, not to cut it," Gates said. "Right now, the bold act of leadership is to defend spending on key international programs, not to attack it."
Gates told Reuters the U.S. government needed to do a better job of promoting the results of overseas aid to a public unnerved by budget cuts at home.
"If you say to the American public, 'What do you think about foreign aid?,' they can have an image from the past where in the Cold War we sent a lot of money to people more for strategic friendship than expecting there to be a benefit to the population in those countries," Gates said.
"If you say to the public, 'What do you think about polio eradication?' ... I don't think you'd get many no's."