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.
