General Motors said on Wednesday that Venezuelan authorities had illegally seized its plant in the industrial hub of Valencia and vowed to "take all legal actions" to defend its rights.
The seizure comes amid a deepening economic crisis in leftist-led Venezuela that has already roiled many US companies.
"Yesterday, GMV's (General Motors Venezolana) plant was unexpectedly taken by the public authorities, preventing normal operations. In addition, other assets of the company, such as vehicles, have been illegally taken from its facilities," the company said in a statement.
It said the seizure would cause irreparable damage to the company, its 2,678 workers, its 79 dealers and to its suppliers.
Venezuela's Information Ministry did not immediately respond to a request for information.
Venezuela's car industry has been in freefall, hit by a lack of raw materials stemming from complex currency controls and stagnant local production, and many plants are barely producing at all.
In early 2015, Ford Motor wrote off its investment in Venezuela when it took an $800 million pre-tax writedown.
The country's economic crisis has hurt many other US companies, including food makers and pharmaceutical firms. A growing number are taking their Venezuelan operations out off their consolidated accounts.
Venezuela's government has taken over factories in the past. In 2014 the government announced the "temporary" takeover of two plants belonging to U.S. cleaning products maker Clorox Co which had left the country.
Venezuela faces around 20 arbitration cases over nationalisations under late leader Hugo Chavez.