We conducted a survey of rodents and ticks in Brazos County in east-central Texas to learn more about native fauna that may be involved in enzootic transmission of pathogens that can cause tick-borne diseases in this region. Our objectives were to describe the species richness and seasonal activity of rodents, as well as to document their infestation with ticks over time. We captured 5 rodent species over the course of 19 months: Sigmodon hispidus (Hispid Cotton Rat), Reithrodontomys fulvescens (Fulvous Harvest Mouse), Peromyscus leucopus (White-footed Mouse), Peromyscus gossypinus (Cotton Mouse), and Baiomys taylori (Northern Pygmy Mouse). We observed a large increase in Hispid Cotton Rat capture success in the fall of 2013, reflecting a characteristic population boom periodically exhibited by this species. Overall tick-infestation prevalence of rodents was low (2.3%), and was comprised of juvenile ticks of 2 species—Amblyomma maculatum (Gulf Coast Tick) and Ixodes scapularis (Blacklegged Tick). The co-occurrence of tick vectors and rodent species that are known reservoirs of tick-borne pathogens underscores the importance of studies to assess tick-borne disease risk in the region.