Federal prosecutors said brothers Eric and Ryan Jensen were arrested on misdemeanor charges of introducing adulterated food into interstate commerce.
The Jensens' attorney did not immediately return a call seeking comment.
Prosecutors said the federal Food and Drug Administration and the Centers for Disease Control determined that the Jensen's didn't adequately clean the cantaloupe.
The FDA has said the melons likely were contaminated in Jensen Farms' packing house. It concluded that dirty water on a floor, and old, hard-to-clean equipment probably were to blame.
The outbreak was the deadliest outbreak of foodborne illness in 25 years. The CDC said people living in 28 states consumed contaminated cantaloupe.
A number of lawsuits were filed by people who were sickened or who had a family member die after the outbreak.
Eric Jensen, 37, and Ryan Jensen, 33, operated their farm in southeastern Colorado. The farm filed for bankruptcy after the outbreak.
The FDA said Jensen Farms had bought the used processing equipment just before the outbreak, and it was corroded, dirty and hard to clean. The packing facility floors also constructed were so they were hard to clean, so pools of water potentially harboring the bacteria formed close to the packing equipment, according to the FDA.
The dirty equipment previously was used to wash and dry potatoes, the agency said, and the listeria could have been introduced as a result of its past use.
The FDA said the way the cantaloupes were cooled after being picked may have exacerbated the listeria growth, and that another possible source of contamination was a truck that frequently hauled cantaloupe to a cattle operation and was parked near the packing house.