"The United States is all in on Africa, and all in with Africa", she said during a visit to Senegal, the start of her three-nation tour on the continent.
"Our engagement is not transactional, it's not for show, and it's not for the short-term."
In Dakar, Yellen described U.S. plans to partner with African countries on climate change, health and security issues.
She reiterated U.S. support for the African Union to join the G20.
She said international institutions needed to be reformed, but also that African governments needed greater accountability and transparency.
"Countries need to be wary of shiny deals that may be opaque and ultimately fail to actually benefit the people they were purportedly designed to help in the first place," Yellen said.
"This can leave countries with a legacy of debt, diverted resources, and environmental destruction."
On Friday, she said the United States had outlined a new strategy towards the continent, seeking "to modernize our relationship by focusing on what we can do together, rather than what we can do for each other".
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Russian Oil Price Cap Could Save Africa Billions: Yellen
Yellen cited the COVID-19 pandemic and Russia's invasion of Ukraine as major economic headwinds for Africa.
"Let me be clear: the single best thing we can do to help the global economy is to end Russia's illegal and unprovoked war in Ukraine," she said.
"Russia's war and weaponization of food has exacerbated food insecurity and caused untold suffering."
The Russian attack upon Ukraine sent world food prices soaring because of disruptions of normal grain shipments from both nations. It took a negotiation with Russia to allow the resumption of grain movement on the Black Sea.
Within Africa, she highlighted a need for greater accountability and transparency from governments.
"Countries need to be wary of shiny deals that may be opaque and ultimately fail to actually benefit the people they were purportedly designed to help in the first place," Yellen said.
"This can leave countries with a legacy of debt, diverted resources, and environmental destruction."
In an implicit contrast with China, which takes a hands-off approach in countries where it invests, Yellen said the US prioritizes "transparency, good governance, accountability, and environmental sustainability."
Along with meetings with Senegal's Minister of Finance Mamadou Moustapha Ba and President Macky Sall, she is scheduled to remain in that West African nation until Sunday, when she is slated to go to Lusaka, Zambia.
Her third African nation on the list is South Africa.
In August, the U.S. Secretary of State and Ambassador to the United Nations Linda Thomas-Greenfield both made multi-country tours of Africa.
They followed an Africa tour by Russian Foreign Minister Sergey Lavrov.
This report was prepared with data from Agence France-Presse with original content by VOA's Jeffrey Young.