Background <p>Methicillin-resistant Staphylococcus aureus is a major cause of healthcare- associated and community-acquired infections. In Ethiopia especially in West hararghe Zone, there is limited data on Methicillin-resistant Staphylococcus aureus among school children in our study setting.</p> Objective <p>To determine the prevalence of <i>Staphylococcus aureus</i> and Methicillin-resistant <i>Staphylococcus aureus</i>, assess their antimicrobial resistance patterns, and identify associated factors among elementary school children in Chiro Town, Ethiopia, from March 15 to June 30, 2024.</p> Methods <p>A community-based cross-sectional study was conductedon 793 primary school children at Chiro town, eastern Ethiopia. Nasal swabs were collected using sterile cotton swabs and transported in labeled Tryptose soya broth. Samples were inoculated onto Mannitol salt agar and blood agar, and then incubated at 37&#xa0;°C for 24&#xa0;h. Isolates were identified using standard microbiological methods. Antibiotic susceptibility was assessed using the Kirby-Bauer disk diffusion method on Mueller-Hinton agar. Cefoxitin-resistant strains were confirmed as MRSA. Data were entered into EPI-Info version 7 and analyzed using SPSS version 20. Logistic regression identified factors associated with MRSA colonization, with statistical significance set at <i>p</i> &lt; 0.05.</p> Results <p>A total of 793 primary school children participated, with a male majority (54%) and most aged 10–15 years (60%). The prevalence of nasal <i>Staphylococcus aureus</i> and <i>Methicillin-resistant Staphylococcus aureus</i> colonization was 16.9% (134/793; 95% CI: 14.3–19.5) and 2.27% (18/793; 95% CI: 1.23–3.31), respectively. For <i>Staphylococcus aureus</i>, colonization was significantly higher among children aged 11–15 years (AOR = 1.56, 95% CI: 1.03–2.35, <i>p</i> = 0.036), students in classrooms with &gt; 66 children (AOR = 5.39, 95% CI: 2.65–10.96, <i>p</i> &lt; 0.001), and those with a history of hospitalization (AOR = 5.85, 95% CI: 3.73–9.17, <i>p</i> &lt; 0.001). Larger household size (&gt; 5 members) was protective against colonization (AOR = 0.50, 95% CI: 0.34–0.75, <i>p</i> = 0.001). For <i>Methicillin-resistant Staphylococcus aureus</i>, significant risk factors included recent antibiotic use (AOR = 4.79, 95% CI: 1.85–12.40, <i>p</i> = 0.001) and history of hospitalization (AOR = 2.87, 95% CI: 1.14–7.26, <i>p</i> = 0.025). Antimicrobial susceptibility testing showed high resistance of <i>Staphylococcus aureus</i> isolates to Penicillin (91.8%) and Tetracycline (83.5%), with full susceptibility to Ciprofloxacin and Chloramphenicol. <i>Methicillin-resistant Staphylococcus aureus</i> isolates exhibited high resistance to Penicillin (100%) and Tetracycline (94.4%), but remained highly susceptible to Ciprofloxacin (95%) and Chloramphenicol (94.4%).</p> Conclusion and recommendation <p>The prevalence of <i>Staphylococcus aureus</i> nasal colonization among elementary school children in Chiro Town was relatively common, whereas MRSA colonization was low (2.27%). Older age, larger classroom size, and a history of hospitalization were significantly associated with S. aureus colonization, while hospitalization and recent antibiotic use were significantly associated with MRSA colonization. Both S. aureus and MRSA isolates exhibited high resistance to commonly used antibiotics, particularly penicillin and tetracycline. Strengthening infection prevention and control measures in healthcare settings, promoting rational antibiotic use, reducing classroom overcrowding, and maintaining continuous surveillance of antimicrobial resistance are recommended to limit the spread of S. aureus and MRSA among school children.</p>