Antibiotics’ effect on Mycoplasma pneumoniae (MP) infection still remains controversial. A prospective study of 257 children with MP pneumonia during a recent epidemic (2015–2016) was conducted. All MP pneumonia patients were treated with corticosteroids within 24–36 h after admission. Initially, oral prednisolone (1 mg/kg) or intravenous methylprednisolone (IVMP; 1–2 mg/kg) was administered for mild pneumonia patients, and IVMP (5–10 mg/kg/day) for severe pneumonia patients. If patients showed a persistent fever for 36–48 h or disease progression, additive IVMP (5 mg/kg or 10 mg/kg) was given. Thirty-three percent of patients received only a broad-spectrum antibiotic without a macrolide. The mean age and the male-to-female ratio was 5.6 ± 3.1 years and 1:1, respectively. Seventy-four percent of patients showed immediate defervescence within 24 h, and 96% of patients showed defervescence within 72 h with improvements in clinical symptoms. Three percent of patients (8/257) who received additive IVMP also showed clinical improvement within 48 h without adverse reactions. There were no clinical or laboratory differences between patients treated with a macrolide ( n = 172) and without ( n = 85). Early corticosteroid therapy might reduce disease morbidity and prevent disease progression in MP pneumonia patients without side effects, and antibiotics may have limited effects on MP infection.