Gram-positive bacteria residing in the nasopharynx can lead to severe illnesses in children, such as otitis media, pneumonia, and meningitis. Despite the potential threat, there is a lack of comprehensive data regarding the carriage rates of these bacteria among children in outpatient departments in the study area. This study aimed to assess the nasopharyngeal carriage, antimicrobial resistance patterns, and associated factors of Gram-positive bacteria among children attending the outpatient department at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia. A hospital-based cross-sectional study was conducted from May 1, 2023, to August 30, 2023. A total of 424 nasopharyngeal swab samples were collected using sterile nasopharyngeal swabs, inoculated on Blood Agar and Mannitol Salt Agar plates, and identified through colony morphology, Gram stain, and biochemical tests. Antimicrobial susceptibility of the identified bacterial isolates was determined employing both the Kirby-Bauer and modified Kirby-Bauer methods. D-tests were conducted using clindamycin and erythromycin discs to detect inducible clindamycin resistance, while cefoxitin disc tests were utilized to ascertain methicillin resistance. Data entry was executed using Epi-Data version 4.6, and subsequent analysis was performed utilizing SPSS version 25. Bivariable and multivariable logistic regression analyses were employed to identify associated factors. An adjusted odds ratio at a 95% confidence interval with a P-value of < 0.05 was considered statistically significant. The overall nasopharyngeal carriage rate of Gram-positive bacteria was 296/424 (69.8%, 95% CI: 65.3-74.0). Staphylococcus aureus was the most prevalent 122/424 (28.8%), followed by Streptococcus pneumoniae 92/424 (21.7%). Methicillin resistance was observed in 19/122 (15.6%) of S. aureus and 3/60 (5%) of coagulase-negative staphylococcus (CoNS) species. Inducible clindamycin resistance was 10/122 (8.2%) in S. aureus and 4/53 (7.5%) in coagulase-negative staphylococcus species. Multidrug resistance was found in 146/296 (49.3%, 95% CI: 43.6-55.0) of the isolates. Associated factors with a bacterial carriage were large family size (AOR = 3.061, 95% CI: 1.595-5.874, P = 0.001), having siblings under five years old (AOR = 1.991, 95% CI: 1.196-3.313, P = 0.008), indoor cooking (AOR = 2.195, 95% CI: 1.275-3.778, P = 0.005), an illiterate mother (AOR = 3.639, 95% CI: 1.691-7.829, P = 0.001), and hospital visits (AOR = 2.690, 95% CI: 1.405-5.151, P = 0.003). The study found a high nasopharyngeal carriage of Gram-positive bacteria in outpatient children, including notable levels of methicillin-resistant S. aureus and multi-drug-resistant isolates. Clindamycin, rifampin, and erythromycin were the most effective antimicrobials for the tested isolates. Factors contributing to bacterial carriage include visits to healthcare facilities, larger family sizes, having younger siblings, maternal illiteracy, and indoor cooking. This emphasizes the need for methicillin-resistant S. aureus surveillance in pediatric outpatient settings and community health education, especially for children's guardians. Additionally, improving household ventilation by separating kitchens from sleeping areas and regular screening of younger siblings in healthcare environments were recommended to reduce bacterial transmission within family members. The study also called for studies with advanced procedures like minimum inhibitory concentration testing and molecular characterization to better comprehend the resistance patterns and genes in circulating bacteria.