Secretary Blinken said in Pretoria Monday that the United States did not see the region as the "latest playing field in a competition between great powers".
"That is fundamentally not how we see it. It's not how we will advance our engagement here," Blinken told a press briefing, speaking alongside his local counterpart Naledi Pandor.
The top U.S. diplomat added "What we seek most of all is a true partnership between the United States and Africa. We don't want an imbalanced or transactional relationship."
"Our commitment to a stronger partnership with Africa is not about trying to outdo anyone else."
His comments came ahead of a policy announcement on the US government's new Africa strategy, which Blinken set forth in a speech at the University of Pretoria later on Monday, in which he said "The U.S. will not dictate Africa's choices."
For his first stop on his three-nation Africa tour, the US top diplomat chose South Africa, a leader in the developing world which has remained neutral in the Ukraine war.
Pretoria has refused to join Western calls to condemn Moscow, which had opposed apartheid before the end of white-minority rule in 1994.
Vulnerable countries in Africa and elsewhere in the world have been hard hit by the fallout from the Ukraine war that has sent prices of fuel and food soaring.
Powerhouse South Africa belongs to a group of emerging economies called BRICS.
In June, Russian President Vladimir Putin urged BRICS countries -- Brazil, Russia, India, China and South Africa -- to cooperate in the face of "selfish actions" from the West.