Citrus maxima Merr. (Pomelo) is a plant with potential antibacterial activity against a broad spectrum of bacterial pathogens. The key active compound is limonene which is a major constituent in the fruit peel. This study investigated the antibacterial activity of C. maxima essential oil (CMEO) against methicillin-resistant Staphylococcus aureus (MRSA). The antibacterial activity was determined by the agar disk diffusion and broth macrodilution methods against S. aureus ATCC 25923 (methicillin-susceptible S. aureus; MSSA), S. aureus ATCC 43300 (MRSA) and 10 clinical isolates of MRSA. The bacteria-killing rate of 1 x MIC CMEO at different exposure times was also evaluated by the time-kill assay. The inhibition zones of CMEO against S. aureus ATCC 25923, S. aureus ATCC 43300 and MRSA isolates were 10.0, 9.0 and 9.9 mm, respectively, but no zone was observed for DMSO control, thus indicating a weak activity of CMEO. The inhibition zone of CMEO against MRSA isolates was significantly different from that of limonene (p < 0.05), indicating a synergistic effect of limonene with other minor compounds in CMEO. The MIC value of CMEO to S. aureus ATCC 43300 was lower than that of S. aureus ATCC 25923 (4.0 vs. 10.7 mg/mL; p < 0.05). The MIC value of CMEO against MRSA isolates was 8.1 ± 4.8 mg/mL with MIC indexes less than 4. In addition, CMEO completely killed both MSSA and MRSA within 4 and 8 hours, respectively. These findings demonstrated the bactericidal effect of CMEO against MRSA, thus it has potential to be developed as a novel antibacterial agent.