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This study examined metropolitan and rural differences regarding concerns about opioid misuse and support for different strategies to reduce opioid use disorder risk in areas not designated as high-risk. This study used cross-sectional data from a regional community health assessment, which was collected in 2019 using a combination of stratified random sampling and clinic-based purposive sampling in Central Texas. The secondary data included 430 and 270 respondents from metropolitan and rural (not metropolitan) counties, respectively. The primary outcomes were perceived concern about the opioid crisis, perceived likelihood of getting addiction treatment, and support for strategies to reduce opioid use disorder risks. Multiple multivariable regression models were used to examine metropolitan and rural differences in the outcome variables after adjusting for age, sex, ethnicity, race, marital status, education, and household income. Respondents were about 58 years old on average. A majority were female (60%), non-Hispanic (88%), and White (83%). About 60% of rural and metropolitan respondents were concerned about opioid use and misuse in their community. After adjusting for respondents’ demographic characteristics, rural respondents were significantly less likely to perceive that individuals are getting the needed opioid use disorder treatment (aOR = 0.69, P = 0.031). Rural respondents were also significantly less supportive for legalizing syringe service programs in their communities (aOR = 0.71, P = 0.044) than metropolitan respondents. Differing attitudes by respondents from metropolitan and rural areas indicate the importance of tailoring prevention and mitigation efforts to address opioid use disorder in advance of an impending public health crisis.