Uruguay traditionally has had strong political and cultural links with its neighbors and Europe. With globalization and regional economic problems, its links to North America have strengthened. Uruguay is a strong advocate of constitutional democracy, political pluralism, and individual liberties. Its international relations historically have been guided by the principles of nonintervention, multilateralism, respect for national sovereignty, and reliance on the rule of law to settle disputes. Uruguay's international relations also reflect its drive to seek export markets and foreign investment. It is a founding member of MERCOSUR. In June 1991, MERCOSUR and the United States signed the Rose Garden Agreement (also known as the "Four Plus One" Agreement). The agreement was non-operational until June 2001 when MERCOSUR invited the U.S. to discuss the feasibility of market access negotiations. The first U.S.-MERCOSUR meeting was held on September 24, 2001, and resulted in the creation of four working groups on industrial trade, e-commerce, agriculture, and investment.

Uruguay is a member of the Rio Group, an association of Latin American states that deals with multilateral security issues (under the Inter-American Treaty of Reciprocal Assistance). Uruguay's location between Argentina and Brazil makes close relations with these two larger neighbors and MERCOSUR associate members Chile and Bolivia particularly important. An early proponent of the Enterprise for the Americas Initiative, Uruguay has actively participated in the follow-up process to the periodic Summits of the Americas, especially the Free Trade Area of the Americas (FTAA). Often considered a neutral country and blessed with a professional diplomatic corps, Uruguay is often called on to preside international bodies. Most recently, Uruguay was selected to chair the FTAA and WTO agricultural committees and an Uruguayan presides over the WTO General Assembly. Uruguay also is a member of the Latin American Integration Association (ALADI), a trade association based in Montevideo that includes 10 South American countries plus Mexico and Cuba.

Disputes - international: Uncontested dispute with Brazil over certain islands in the Quarai/Cuareim and Invernada streams and the resulting tripoint with Argentina.