The Council of Central American Ministers of Trade meets on a regular basis to work on regional approaches to trade issues. The council signed a Trade and Investment Framework Agreement (TIFA) with the U.S. in 1998, and was part of the negotiations that led to the creation of CAFTA. Guatemala joined Honduras and El Salvador in signing a free trade agreement with Mexico in 2000, which went into effect the following year. Guatemala also originated the idea for, and is the seat of, the Central American Parliament (PARLACEN).

President Bill Clinton and the Central American presidents signed the CONCAUSA (Conjunto Centroamerica-USA) agreement at the Summit of the Americas in December 1994. CONCAUSA is a cooperative plan of action to promote clean, efficient energy use; conserve the region's biodiversity; strengthen legal and institutional frameworks and compliance mechanisms; and improve and harmonize environmental protection standards.

Guatemala has a long-standing claim to a large portion of Belize; the territorial dispute caused problems with the United Kingdom and later with Belize following its 1981 independence from the U.K. In December 1989, Guatemala sponsored Belize for permanent observer status in the Organization of American States (OAS). In September 1991, Guatemala recognized Belize's independence and established diplomatic ties, while acknowledging that the boundaries remained in dispute. In anticipation of an effort to bring the border dispute to an end in early 1996, the Guatemalan Congress ratified two long-pending international agreements governing frontier issues and maritime rights. In 2001, Guatemala and Belize agreed to a facilitation process led by the OAS to determine the land and maritime borders separating the two countries. National elections in Guatemala put a temporary halt to progress, but discussions will resume at a bilateral meeting on the margins of the Summit of the Americas in early November 2005 and a Foreign Minister-level meeting November 14-15, 2005 in San Pedro, Belize.