Assistant Secretary of State Daniel Russel said the comments were creating "a climate of uncertainty" about the Philippines' intentions.
Mr Duterte has announced a "separation from the US", its longstanding ally.
It follows US criticism of the Philippines' brutal war against drugs.
The campaign has caused thousands of extrajudicial killings.
Mr Russel said the US was concerned about the loss of life in Mr Duterte's crackdown on the drugs trade.
"I pointed out to secretary [Foreign Minister Perfecto] Yasay that the succession of controversial statements and comments and a real climate of uncertainty about the Philippines' intentions has created consternation in a number of countries, not only in mine," Mr Russel said.
"This is not a positive trend. And as I candidly shared with the foreign secretary, your friends are also concerned about the loss of life in connection with the counter-narcotics campaign."
The US called for clarification after President Duterte addressed an economic forum in China last week, saying: "I announce my separation from the United States. Both in military, not maybe social, but economics also. America has lost."
He added: "I've realigned myself in your ideological flow and maybe I will also go to Russia to talk to [President Vladimir] Putin and tell him that there are three of us against the world - China, Philippines, and Russia. It's the only way."
US officials said the remarks were "at odds" with the "close relationship" shared by the countries.
Mr Russel said that although the US welcomed improved ties between the Philippines and China, it should not come at the expense of the US or other nations.
"It's a mistake to think that improved relations between Manila and Beijing somehow come at the expense of the United States. This should be addition and not subtraction," he said.
Mr Duterte has grown increasingly hostile towards the US since taking office in June.
He has said he wants to end joint military exercises with the US and told President Barack Obama he could "go to hell" after criticism over his bloody war against drugs.
Philippines President Rodrigo Duterte's recent statements have caused "consternation" in the US and other nations, the most senior US diplomat for Asia said during a visit to Manila.