Secretary of State Hillary Clinton said "these appalling assaults on members of our own State Department family are, sadly, part of a growing tragedy besetting many communities in Mexico."
"They underscore the imperative of our continued commitment to work closely with the Government of President Calderon to cripple the influence of trafficking organizations at work in Mexico," she added. "This is a responsibility we must shoulder together."
Calderon's office said the Mexican president "expresses his indignation" and "his sincerest condolences to the families of the victims." He "reiterated the Mexican government's unwavering compromise to resolve these grave crimes."
U.S. Rep. Silvestre Reyes, who represents El Paso, expressed concern about the safety of Americans who frequently cross into Ciudad Juarez to work or visit relatives.
"These brutal murders are another sobering reminder that Mexico's drug-related violence poses a shared security threat to the United States," Reyes said in a statement. "Many American citizens and innocent civilians have lost their lives in drug-related violence, and thousands of El Pasoans continue to live and work in Ciudad Juarez every day."
Some Americans killed have been involved in the drug trade. Other cases have not been resolved, including the December killing of Augustin Salcedo, a California school board member and assistant principal who was abducted with five other men from a restaurant in northern Durango state.
Nearly 18,000 people have been killed since Calderon deployed tens of thousands of troops and federal police across the country in December 2006 in an offensive against drug traffickers.
In Acapulco, a battle between drug gangs killed eight gunmen and a 23-year-old woman caught in the cross fire as she rode in a taxi, according to a Guerrero state police report.
Weekend shootouts left more than 30 people dead in Guerrero, where several cartels are battling for drug dealing turf and trafficking routes. Eight people were killed Friday night when gunmen burst into party in western Sinaloa state.
Associated Press writers Philip Elliott in Washington and Terry Wallace in Dallas contributed to this report.