China is accused of mass detentions, religious persecution and forced sterilisation of Uighurs and others.
The sanctions target the US-connected financial interests of regional Communist Party boss Chen Quanguo and three other officials.
China denies any mistreatment of Muslims in far-western Xinjiang.
Authorities there are thought to have detained about a million people in re-education camps in recent years. They say “vocational training” is needed to counter radicalism and separatism.
Mr Chen, who sits on the Chinese Communist Party’s powerful Politburo, is the highest-ranking Chinese official ever to be hit by US sanctions, the Trump administration says. He is seen as the architect of Beijing’s policies against minorities, and was previously in charge in Tibet.