A two decades-long epidemic of Rocky Mountain spotted fever in northern México reached the U.S. border city of Tijuana in 2021. Cases were near the city periphery in marginalized areas, some lacking infrastructure such as streets or utilities. We worked in the three census areas where human cases were reported and in 12 additional control Áreas Geoestadisticas Básicas. There were dogs, the primary tick host and Rickettsia rickettsii reservoir, in 76% of homes, with 2.2 owned dogs per home on average, approximately equal numbers of roaming dogs were seen, and 46.2% of owned dogs were allowed to roam in the street. Sixty-eight percent of people had heard of Rocky Mountain spotted fever (RMSF), and 35% self-reported tick infestation, including 19% of homes without dogs. Ticks appeared to move among houses of adjacent neighbors. Of 191 examined dogs, 61.8% were tick-infested, with 6-fold increased odds if they were allowed to roam. Although no dogs were Rickettsia polymerase chain reaction-positive, we found one R. rickettsii- and 11 Rickettsia massiliae-infected ticks. The rickettsial IgG seroprevalence by immunofluorescence antibody assay was 76.4%, associated with unhealthy body condition, adults, dogs with >10 ticks, more dogs being seen in the area, and dogs being permitted in the street. Insufficient medical and canine management resources have contributed to a case fatality rate of RMSF that has exceeded 50% in areas. High canine seroprevalence suggests risks to people and dogs; unfortunately, herd immunity is impeded by high turnover in the canine population owing to the birth of puppies and high death rates. Binational One Health workers should monitor disease spread, enact canine population management and tick eradication, and provide prevention, diagnostic, and treatment support.