WASHINGTON—The Trump administration suspended all commercial passenger and cargo flights between the U.S. and Venezuela, citing safety concerns stemming from political instability and economic turmoil in the South American nation.

Acting Secretary of Homeland Security Kevin K. McAleenan determined that “conditions in Venezuela threaten the safety and security of passengers, aircraft, and crew, requiring an immediate suspension,” the Department of Homeland Security said. Secretary of State Mike Pompeo then approved the flight suspension and Transportation Secretary Elaine Chao implemented it, officials said.

The order from Ms. Chao cites violence in and around Venezuelan airports, U.S. officials’ inability to access the airports and verify their security procedures, flight suspensions by major carriers and a Federal Aviation Administration order earlier this month barring U.S. aircraft from flying below 26,000 feet over Venezuelan territory.

The measure will further disconnect a country engulfed in social unrest and suffering an unprecedented economic contraction as governments around the region step up pressure on the authoritarian regime of President Nicolás Maduro.

Venezuelans have clashed in the streets with pro-government forces following a call by opposition leader Juan Guaidó to overthrow Mr. Maduro’s government. Mr. Guaidó is recognized by the U.S. as Venezuela’s legitimate leader following a 2018 election that was marred by fraud allegations.