Neonatal abstinence syndrome (NAS) has increased over the last 2 decades, but limited data exist on its association with economic conditions or clinician supply. To determine the association among long-term unemployment, clinician supply (as assessed by primary care and mental health clinician shortage areas), and rates of NAS and evaluate how associations differ based on rurality. Ecological time-series analysis of a retrospective, repeated cross-sectional study using outcome data from all 580 counties in Florida, Kentucky, Massachusetts, Michigan, New York, North Carolina, Tennessee, and Washington from 2009 to 2015 and economic data from 2000 to 2015. Negative binomial models were used with year and county-level fixed effects. Interactions were tested and stratified analyses were conducted by metropolitan counties, rural counties adjacent to metropolitan counties, and rural remote counties. County-level 10-year unemployment rate and mental health and primary care clinician supply obtained from the Health Resources and Services Administration Area Health Resources Files. Rates of NAS, excluding iatrogenic withdrawal, obtained from state inpatient databases. The sample included observations from 580 counties over 7 years (1803 county-years from metropolitan counties, 1268 county-years from rural counties adjacent to metropolitan counties, and 927 county-years from rural remote counties). During the study period, there were 6 302 497 births and 47 224 diagnoses of NAS. The median rate of NAS was 7.1 per 1000 hospital births (interquartile range [IQR], 2.2-15.8), the 10-year unemployment rate was 7.6% (IQR, 6.4%-9.0%), and 83.9% of county-years were partial or complete mental health shortage areas. In the adjusted analyses, mental health shortage areas had higher NAS rates (unadjusted rate in shortage areas of 14.0 per 1000 births vs unadjusted rate in nonshortage areas of 10.6 per 1000 births; adjusted incidence rate ratio [IRR], 1.17 [95% CI, 1.07-1.27]), occurring primarily in metropolitan counties (adjusted IRR, 1.28 [95% CI, 1.16-1.40]; P = .02 for test of equivalence between metropolitan counties and rural counties adjacent to metropolitan counties). There was no significant association between primary care shortage areas and rates of NAS. The 10-year unemployment rate was associated with higher rates of NAS (unadjusted rate in highest unemployment quartile of 20.1 per 1000 births vs 7.8 per 1000 births in lowest unemployment quartile; adjusted IRR, 1.11 [95% CI, 1.00-1.23]) occurring primarily in rural remote counties (adjusted IRR, 1.34 [95% CI, 1.05-1.70]; P = .04 for test of equivalence between metropolitan counties and rural remote counties). In this ecological analysis of counties in 8 US states, there was a significant association among higher long-term unemployment, higher mental health clinician shortage areas, and higher county-level rates of neonatal abstinence syndrome.