Moldovan anti-corruption prosecutors have charged Plahotniuc, who fled the country in June when the PDM-led government collapsed, with organizing a criminal network used to trade illicit goods and with laundering millions of dollars between 2013 and 2015.
"In his official capacity, Plahotniuc was involved in corrupt acts that undermined the rule of law and severely compromised the independence of democratic institutions in Moldova," Secretary of State Mike Pompeo said in the statement.
The ban also includes Plahotniuc's wife, Oxana, and their two children.
Plahotniuc's critics say he once wielded overwhelming control over Moldova's politics and economy. His location is unknown, but media reports say he may have fled to the United States.
Plahotniuc is also wanted by Russia on drug trafficking and homicide charges.
Plahotniuc left the country after the pro-European ACUM bloc agreed to form a coalition with President Igor Dodon's pro-Russia Socialist Party (PSRM) on June 8, pushing the ruling PDM out of government.
The ACUM-PSRM coalition collapsed in a no-confidence vote in November, prompting Dodon to appoint a technocrat government backed in parliament by the PDM and the PSRM.
Moldova has been dogged by political instability and corruption ever since it declared independence from the Soviet Union in 1991, and hundreds of thousands of Moldovans have left the country.
The disappearance in 2014 of some $1 billion, or about one-eighth of Moldova's gross domestic product, from its banking system sparked a wave of public outrage. Plahotniuc's critics say he was involved in what came to be known as "the theft of the century."