In the past 10–15 years, the government of China has made various efforts in tackling excessive antibiotics use. Yet, little is known about their effects at rural primary care settings. This study aimed to determine the impact of government policies and the COVID-19 pandemic on antibiotic prescribing practices at such settings utilizing data from separate studies carried out pre- and during the pandemic, in 2016 and 2021 in Anhui province, China, using identical sampling and survey approaches. Data on antibiotics prescribed, diagnosis, socio-demographic, etc., were obtained through non-participative observation and a structured exit survey. Data analysis comprised mainly descriptive comparisons of 1153 and 762 patients with respiratory infections recruited in 2016 and 2021, respectively. The overall antibiotics prescription rate decreased from 89.6% in 2016 to 69.1% in 2021, and the proportion of prescriptions for two or more classes of antibiotics was estimated as 35.9% in 2016 and 11.0% in 2021. There was a statistically significant decrease in the number of days from symptom onset to clinic visits between the year groups. In conclusion, measures to constrain excessive prescription of antibiotics have led to some improvements at the rural primary care level, and the COVID-19 pandemic has had varying effects on antibiotic use.