He criticized the U.S. government for not focusing more on treatment and prevention and said easing drug laws would result in "serious consequences for American and Mexican society."
"Drugs kill in production. Drugs kill in distribution, as is the case in the violence in Mexico, and drugs kill in consumption," Calderon said.
The Obama administration disputed Calderon's claims of a softening stance on drugs. Gil Kerlikowske, the administration's drug czar, said he and the president have repeatedly expressed their opposition to legalization.
"We could not be clearer about why we oppose this for a whole host of really good reasons," Kerlikowske said.
Even some who back sweeping reform of drug laws doubt that voter approval of the California measure would yield quick results in Mexico's brutal drug war. But it would probably throw fuel on the debate south of the border.
Jorge Hernandez Tinajero, president of a Mexico City-based group that favors drug law reform, said that although polls in Mexico have shown little support for making drugs legal, that could change if California votes yes and advocates recast the question into one of safety.
"If you tell them it will reduce violence in Mexico, the vast majority of people would say yes," he said.
Ellingwood reported from Mexico City and Marosi from Tijuana. Times staff writer John Hoeffel in Los Angeles contributed to this report.