The announcement raised international tension over Venezuela, where political unrest has left 28 people dead this month.
Venezuela said on Wednesday it was withdrawing from the Organization of American States, a regional bloc of 35 member states.
Venezuela said the move was a response to a Washington-backed campaign against the ruling Socialist Party that is meant to trample on the sovereignty of Venezuela, the United States' principal ideological adversary in the region.
"Tomorrow, as ordered by President Nicolas Maduro, we will present a letter of resignation from the Organization of American States, and we will begin a procedure that will take 24 months," Foreign Minister Delcy Rodriguez said in a televised statement.
The announcement raised international tension over Venezuela, where unrest has left 28 people dead this month.
Echoed by the United States and European Union, the OAS has led an international chorus of concern over the economic and political chaos in the major oil-exporting country.
The OAS agreed on Wednesday to hold a meeting of foreign ministers to discuss the situation in Venezuela.
Maduro had warned on Tuesday that Venezuela would quit the group if the meeting were called.
Critics of President Nicolas Maduro have said Venezuela could be expelled from the group, accusing his government of eroding the country's democracy by delaying elections and refusing to respect the opposition-led Congress.
The decision extends Venezuela's drift toward the fringes of international diplomacy.
But the limited influence of the OAS means its exit will have few economic implications for the OPEC nation that is already struggling under triple-digit inflation, chronic product shortages and a crippling recession.
More than 15 years of diplomatic tensions between Caracas and Washington have done little to disrupt the flow of oil and fuel toward US shores.
The OAS, once dominated by influential leftist governments from countries such as Argentina and Brazil, has clashed for months with Venezuela.
Recent changes in governments in both countries brought in leaders openly hostile toward Maduro.
OAS chief Luis Almagro has said Venezuela should be suspended if it does not hold general elections "as quickly as possible."
Maduro's government calls the OAS a pawn of US policy and dismisses Almagro, a former Uruguayan foreign minister once friendly with Venezuela's socialists, as a turncoat working for Washington.