Dr Anthony Fauci said the Delta variant of Covid-19 was driving the spike in areas with low vaccination rates.
He said health officials were considering revising mask guidance for vaccinated Americans to curb cases.
Offering booster jabs to vulnerable people was also under review, he said.
The coronavirus situation in the US is becoming "a pandemic among the unvaccinated", Dr Fauci, the chief medical adviser to US President Joe Biden, told broadcaster CNN on Sunday.
More than 162.7 million people - or 49% of the population - have been fully vaccinated in the US, official data shows.
The US had been a world leader in jab uptake until April, when vaccination rates started to drop off.
Vaccination rates are particularly low in southern states, where fewer than half of residents have received their first dose in some cases.
Meanwhile, daily coronavirus infections are on the rise again after numbers fell in May and June.
The resurgence has added to the more than 34 million cases and 610,000 deaths recorded so far in the US.
The trend has been attributed, in part, to the rapid spread of the highly transmissible Delta variant of Covid.