Mycoplasma pneumoniae, a major etiological agent of community-acquired pneumonia, exhibits distinct cyclic epidemic patterns recurring every three to five years. Several cases of co-infection with severe acute respiratory syndrome coronavirus 2 have been reported globally, resulting in unfavorable clinical manifestations. This study investigated the epidemiological features of the recent M. pneumoniae outbreak (May 2019–April 2020) using retrospective data from the last five years. Molecular test data for macrolide resistance and co-infection were obtained from the Seegene Medical Foundation. National medical expenditure and hospitalization rates were analyzed using data from The Health Insurance Review and Assessment Service of Korea. The macrolide resistance rate was 69.67%, peaking at 71.30% during the epidemic period, which was considerably higher than the 60.89% rate during non-epidemic periods. The co-infection rate with other respiratory pathogens was 88.49%; macrolide-resistant M. pneumoniae strains showed a 2.33% higher co-infection rate than the susceptible strains. The epidemic period had 15.43% higher hospitalization and 78.27% higher medical budget expenditure per patient than non-epidemic periods. The increased rates of macrolide resistance and co-infection observed in macrolide-resistant M. pneumoniae during the epidemic period highlight the importance of monitoring future outbreaks, especially considering macrolide resistance and the risk of co-infection with other pathogens.