"U.S. citizens residing or travelling in Russia should depart immediately," the U.S. embassy in Moscow said. "Exercise increased caution due to the risk of wrongful detentions."
"Do not travel to Russia," it added.
"Russian security services have arrested U.S. citizens on spurious charges, singled out U.S. citizens in Russia for detention and harassment, denied them fair and transparent treatment, and convicted them in secret trials or without presenting credible evidence," the embassy said.
"Russian authorities arbitrarily enforce local laws against U.S. citizen religious workers and have opened questionable criminal investigations against U.S. citizens engaged in religious activity."
The Kremlin said it was not the first time U.S. citizens had been asked to leave Russia. The last such public warning was in September after President Vladimir Putin ordered a partial mobilization.
"They (warnings) have been voiced by the State Department many times in the last period, so this is not a new thing," Kremlin spokesman Dmitry Peskov told reporters.
Moscow's Federal Security Service (FSB) said in January that prosecutors had opened a criminal case against a United States citizen on suspicion of espionage.
Last December, U.S. basketball star Brittney Griner was released in a prisoner swap, having been sentenced to nine years in a penal colony for possessing vape cartridges containing cannabis oil - which is banned in Russia - after a judicial process labelled a sham by Washington.