Objectives This study aimed to investigate the clinical characteristics and risk factors of severe macrolide-resistant Mycoplasma pneumoniae pneumonia (MRMP) induced by the 23 S rRNA A2063G mutation. Methods Clinical data were collected from 526 pediatric patients diagnosed with Mycoplasma pneumoniae pneumonia (MPP) at Kunming Children's Hospital, representing a single-center cohort study conducted between October 2023 and February 2024. Among them, 483 cases (91.83%) tested positive for the 23 S rRNA A2063G mutation. Patients were categorized into severe (n = 192) and general (n = 291) groups based on clinical severity. Univariate and multivariate logistic regression analyses were performed to identify risk factors for severe MRMP. Results Univariate analysis revealed that the severe group had younger age, longer disease duration, higher peak fever temperatures, and prolonged fever duration compared to the general group. The incidence of wheezing, dyspnea, and decreased breath sounds was significantly higher in the severe group. Radiological findings indicated a higher prevalence of pulmonary consolidation, atelectasis, pleural effusion, and multi-lobar involvement in the severe group. Laboratory tests showed elevated levels of neutrophils, platelets, liver enzymes, lactate dehydrogenase (LDH), D-dimer, and erythrocyte sedimentation rate, alongside reduced levels of albumin, blood urea nitrogen, and creatinine in the severe group. Regarding treatment, doxycycline was the primary alternative for MRMP, but fluoroquinolones were more frequently administered in the severe group, along with a significantly higher usage of glucocorticoids. Additionally, oxygen therapy was more commonly required in the severe group, with 2% of patients necessitating mechanical ventilation or admission to the pediatric intensive care unit. Compared to the general group, the severe group had significantly longer hospital stays (P < 0.01), prolonged lung rales, slower decline in inflammatory markers, and delayed radiological improvement. However, no fatalities were recorded in this cohort. Multivariate logistic regression analysis identified prolonged fever duration, multi-lobar consolidation, elevated LDH, and increased D-dimer levels as independent risk factors for severe MRMP. Receiver Operating Characteristic (ROC) curve analysis demonstrated that the combination of fever duration, multi-lobar consolidation, LDH, and D-dimer had high sensitivity and specificity for diagnosing severe MRMP, with an area under the curve (AUC) of 0.90. Conclusion Prolonged fever duration, multi-lobar consolidation, elevated LDH, and increased D-dimer levels are key predictive indicators for severe MRMP. Although severe MRMP is associated with a prolonged clinical course and complex treatment, timely adjustment of antibiotic regimens and supportive care can effectively improve outcomes.