Guyana has diplomatic relations with a wide range of nations. The European Union (EU), the Inter-American Development Bank (IDB), the UN Development Program (UNDP), the World Health Organization (WHO), and the Organization of American States (OAS) have offices in Georgetown. The Caribbean Community (CARICOM) has its Secretariat headquartered in Georgetown.

Guyana strongly supports the concept of regional integration. It played an important role in the founding of the Caribbean Community and Common Market (CARICOM), but its status as one of the organization's poorest members limits its ability to exert leadership in regional activities. Guyana has sought to keep foreign policy in close alignment with the consensus of CARICOM members, especially in voting in the UN, OAS, and other international organizations. In 1993, Guyana ratified the 1988 Vienna Convention on illicit traffic in narcotic drugs and cooperates with U.S. law enforcement agencies on counternarcotics efforts.

Two neighbors have longstanding territorial disputes with Guyana. In 1962 Venezuela challenged a previously accepted 1899 international arbitration award, and claimed all of Guyana west of the Essequibo River--62% of Guyana's territory. At a meeting in Geneva in 1966, the two countries agreed to receive recommendations from a representative of the UN Secretary General on ways to settle the dispute peacefully. Diplomatic contacts between the two countries and the Secretary General's representative continue. Neighboring Suriname also claims the territory east of Guyana's New River, a largely uninhabited area of some 15,000 square kilometers (6,000 sq. mi.) in southeast Guyana. Guyana and Suriname also dispute their offshore maritime boundaries. This dispute flared up in June 2000 in response to an effort by a Canadian company to drill for oil under a Guyanese concession. Guyana regards its legal title to all of its territory as sound. In 2004, Guyana took its maritime dispute with Suriname to the Law of the Sea tribunal for arbitration. The decision of the tribunal is still pending.