Eric and Ryan Jensen entered the pleas in federal court in Denver to six counts of introducing adulterated food into interstate commerce. Prosecutors say the brothers agreed to plead guilty without any concessions regarding sentencing.
"These young men are stepping up because it happened on their watch," Forrest Lewis, a lawyer for Eric Jensen, said in court.
A sentencing hearing has been set for Jan. 28. A probation officer will issue a presentence report that will help guide the judge in imposing a sentence.
The charges carry penalties of up to six years in prison and $1.5 million in fines. Lewis said in court that the brothers have no criminal record. The Jensens previously filed for bankruptcy.
Officials have said people in 28 states ate the contaminated fruit and 147 were hospitalized.
A statement from the Jensens' attorneys says the brothers were shocked and saddened by the deaths, but the guilty pleas do not imply any intentional wrongdoing or knowledge that the cantaloupes were contaminated.
Both brothers acknowledged in court that they had processed and shipped tainted cantaloupe in July and August of 2011.
"We were in charge of the operation and we initially shipped a product that was adulterated," Eric Jensen said.
The brothers have sued the safety auditor who gave their farm a "superior" rating just before the outbreak — the deadliest case of foodborne illness in the nation in a quarter century.
The Food and Drug Administration has said the rare move to charge the Jensens was intended to send a message to food producers.
Criminal charges are rare in food-borne illnesses, but under President Barack Obama the FDA has been more aggressive in pursuing farmers and food processors for alleged lapses.
The Jensens' "actions resulted in tragedy nationwide, and profound economic consequences for an entire industry, and has exposed them to these serious criminal consequences," U.S. Attorney John Walsh said after the pleas.
Federal investigators said the melons at Jensen Farms in southeast Colorado likely were contaminated in its packing house because of dirty water on the floor and old, hard-to-clean equipment.
The Jensens filed their lawsuit against PrimusLabs, a Santa Maria, Calif., food safety auditor that checked Jensen Farms in July of 2011.
The Jensens argued that they asked the auditor about a new processing system, which removed a step of rinsing the melons with chlorinated water. The lawsuit states the PrimusLabs auditor "did not warn Jensen that the new system created a hazard or a risk of contamination."
No one answered the phone at a number listed for the company.