In a statement, Blinken said Ambassador Jeffrey Feltman will visit Egypt, Eritrea, Ethiopia and Sudan through May 13.
The special envoy will meet with officials from those governments, as well as the United Nations and the African Union, in addition to political stakeholders and humanitarian groups.
"The special envoy's travel underscores the administration's commitment to lead a sustained diplomatic effort to address the interlinked political, security and humanitarian crises in the Horn of Africa, and he will coordinate U.S. policy across the region to advance that goal," Blinken said.
Former U.S. Ambassador to Ethiopia David Shinn told VOA Monday that Feltman's travel to Eritrea is significant because "it's the first time in a number of years that a senior American official has been allowed to meet with senior Eritrean officials."
"That in itself is a good thing," Shinn said.
The United States has been pressing Ethiopia to end the conflict in its Tigray region, which has been raging for six months. U.S. officials are also calling for allied Eritrean troops to withdraw from the region.
"If they don't return to Eritrea, I think there will be an increasing tendency by the United States to look upon Eritrea as something of a pariah nation in the Horn of Africa," said Shinn, who is now teaching at the Elliott School of International Affairs at George Washington University.
Ethiopia's northern Tigray region has been the epicenter of hostilities since November, when fighters from the Tigray People's Liberation Front (TPLF) attacked army bases in the region, according to the federal government. The attack, Ethiopian Prime Minister Abiy Ahmed said, prompted his government to launch a military offensive to push the group out.
The fighting has left at least 4.5 million people in need of humanitarian assistance in Tigray, according to the interim administration. The United Nations has appealed for $1.5 billion to assist 16 million people in Tigray and across Ethiopia this year.
Separately, tensions have also been rising among Sudan, Egypt and Ethiopia over the Grand Ethiopian Renaissance Dam (GERD), which Ethiopia is building on the Blue Nile, close to the border with Sudan.
Egypt and Sudan want a legal agreement in place with Ethiopia before Addis Ababa begins filling the reservoir behind the mega dam. But Ethiopia began filling it last year, a move the other two countries see as directly threatening their water and electricity supplies.
The African Union has been in the lead trying to resolve the simmering dispute among the three neighbours.