COVID-19, caused by SARS-CoV-2 virus, has disproportionately affected Black and Hispanic communities in the US, which can be attributed to social factors including inconsistent public health messaging and suboptimal adoption of prevention efforts. To identify behaviors and evaluate trends in COVID-19-mitigating practices in a predominantly Black and Hispanic population, to identify differences in practices by self-reported ethnicity, and to evaluate whether federal emergency financial assistance was associated with SARS-CoV-2 acquisition. This survey study was conducted by telephone from July 1 through August 30, 2020, on a random sample of adults who underwent SARS-CoV-2 testing at a safety-net health care system in Chicago during the surge in COVID-19 cases in the spring of 2020. Behaviors and receipt of a stimulus check were compared between participants testing positive and negative for SARS-CoV-2. Differences in behaviors and temporal trends were assessed by race and ethnicity. SARS-CoV-2 infection was assessed using nasopharyngeal quantitative reverse transcriptase-polymerase chain reaction testing. Mitigating behaviors and federal emergency financial assistance were assessed by survey. Race and ethnicity data were collected from electronic health records. Of 750 randomly sampled individuals, 314 (41.9%) consented to participate (169 [53.8%] women). Of those, 159 (51%) self-reported as Hispanic and 155 (49%) as non-Hispanic (120 [38.2%] Black), of whom 133 (84%) and 76 (49%) tested positive for SARS-CoV-2, respectively. For all participants, consistent mask use (public transport: adjusted odds ratio [aOR], 0.00; 95% CI, 0.00-0.34; social gatherings: aOR, 0.10; 95% CI, 0.00-0.50; running errands: aOR, 0.18; 95% CI, 0.07-0.42; at work: aOR, 0.23; 95% CI, 0.07-0.79) and hand sanitizer use (aOR, 0.26; 95% CI, 0.13-0.52) were associated with lower odds of infection. During 3 sampled weeks, mitigation practices were less frequent among Hispanic compared with non-Hispanic participants (eg, mask use while running errands: aOR, 0.26; 95% CI, 0.15-0.46). Hispanic participants were at high risk of infection (aOR, 5.52; 95% CI, 4.30-7.08) and more likely to work outside the home (aOR, 2.05; 95% CI, 1.27-3.30) compared with non-Hispanic participants, possibly because of limited receipt of stimulus checks (aOR, 0.03; 95% CI, 0.02-0.07) or unemployment benefits (aOR, 0.36; 95% CI, 0.16-0.74). In this survey study of adults in a large US city, public health messaging improved preventive behaviors over time but lagged among Hispanic participants; messaging tailored to Hispanic communities, especially for mask use, should be prioritized. Hispanic individuals were at higher risk for infection, more often worked outside the home, and were less likely to have received a stimulus check; this suggests larger studies are needed to evaluate the provision of economic support on SARS-CoV-2 transmission dynamics in low-income populations.