Myrna Mack Chang died of 27 stab wounds in Guatemala City while conducting research about uprooted indigenous victims of military repression at a time when the Central American country was mired in civil war.
The murder occurred six years before the end of the 1960-1996 armed conflict, which left 200,000 dead or missing, according to the United Nations.
Julio Lopez, 50, and Jose Gonzalez, 49, were arrested on charges of crimes against humanity after a series of raids in the departments of Santa Rosa and Jutiapa, police said.
Their arrest was ordered by a Guatemala City court that did not provide details on the roles they were alleged to have played in the murder.
In February 1994, a Guatemalan court sentenced Sergeant Noel de Jesus Beteta, a member of the country's presidential guard, to 25 years in prison over the murder.
In October 2002, another court sentenced Colonel Juan Valencia to 30 years behind bars for ordering the killing. However, the former head of the presidential guard's security department is a fugitive of justice.
In 2004, President Oscar Berger (2004-2008) apologized to Mack Chang's family for the murder on behalf of the state during a public ceremony after being ordered to do so by the Inter-American Court of Human Rights.