The trip, which will take in Ethiopia, the Democratic Republic of Congo and Angola, will seek to "encourage democratic development, promote respect for human rights, advance peace and security," State Department spokeswoman Jen Psaki has said.
Kerry who left for the trip yesterday and is due to return to Washington on May 5, will also "engage with civil society and young African leaders, who will shape the continent's future, and promote trade, investment and development partnerships in Africa."
Ethiopia has been hosting peace talks between South Sudan's government and rebels aimed at ending a bloody four-month civil war, which has left thousands of people dead and over a million displaced.
The talks resumed again on Monday after long delays but have made little progress.
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Kerry is expected to try to press the negotiators to end the fighting amid global outrage over a wave of atrocities in the world's newest nation, which the US helped give birth to.
"We will be delivering tough messages to both sides to indicate... That they will be held accountable if they don't take the necessary actions to end the hostilities," a senior State Department official said.
The official confirmed that Washington was still deciding who should be targeted for sanctions.
"We're working on a list. So that process is moving forward."
Washington would have sought to prevent the conflict which erupted in December if it had been possible, the official said.
"I see them fighting a personal battle that has led to the deaths of many people. This is not a battle against -- Nuer against Dinka. It is a Riek Machar-Salva Kiir battle, and they have used ethnic tensions and their own ethnicity to foment what has been a horrific war in this country.