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.

Joel Richards, 20, was left at Birmingham's City Hospital on Sunday where he died from his injuries.
A 17-year-old boy was arrested on suspicion of murder at a service station on the M40 on Monday evening.
West Midlands Police also stopped a car on the motorway near Oxford and arrested three men and a woman on suspicion of assisting an offender.
Supt Tom Chisholm said:  "This continues to be a fast paced inquiry and we have made five arrests over the bank holiday weekend.
"However, our work is not done and we continue to investigate the circumstances that led to this young man's death.
"We will still continue to liaise with Joel's family and our thoughts remain with them as they continue to come to terms with their loss."

Southampton's second 13-mile event was held on Sunday and attracted more than 6,000 runners.
Race director Chris Rees said there was "definitely a demand" for a 26.2-mile (42km) run at next year's event and one could be formally announced by the autumn.
More than 500 people responded to the suggestion on social media, he added.
Southampton City Council has said it cannot "offer any comment at this early stage", but added it was "delighted" by the recent successes of the half marathon.
The inaugural Southampton half-marathon was held last April, along a route that passes many of the city's landmarks, including the Bargate, St Mary's Stadium and Itchen Bridge.
Organisers said most people who had responded to the suggestion of a full marathon favoured a separate 26-mile route, rather than the idea of running the 13-mile route twice.
Mr Rees said: "This weekend showed how much the city embraces and enjoys running so it would be great to have a marathon in the city - it just has to be done right.
"We've got a couple of ideas and proposals and we want to work with the council, runners and community groups and residents to make sure they are all backing the event."
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.
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Five people have been arrested after a man left at a hospital died of stab wounds.
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Organisers of the Southampton half marathon have said they would like to introduce a full marathon to the city.