Myopia is a growing concern worldwide, especially among adolescents. This study aimed to investigate the prevalence and associated factors of myopia in adolescents aged 12–15 in Shandong Province, China. This cross-sectional study adhered to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines and involved stratified random cluster sampling of 128,678 students from 186 middle schools across 17 cities in Shandong Province. Data collection was conducted from March to April 2024. We excluded students with organic eye diseases, abnormal binocular vision functions, or a history of eye injuries or surgeries. Myopia was assessed using the standard logarithmic visual acuity chart and autorefractor without inducing ciliary muscle paralysis. A comprehensive questionnaire survey was conducted to gather demographic characteristics and daily life behaviors. With the chi-squared test for univariable analysis and multivariable logistic regression for identifying significant factors. This study included 126,375 participants, with a gender distribution of 51.02% male and 48.98% female. The overall prevalence of myopia was 71.34%. Higher prevalence was observed in girls (72.26%) compared to boys (70.45%), and the prevalence increased with age, peaking at 73.12% in 15-year-olds. Urban residents had a higher prevalence (71.86%) than rural (70.39%). Factors such as increased frequency of eye usage while lying down or leaning forward, frequent use of eyes while walking or riding in a car, prolonged screen time, and extended homework duration were associated with higher odds of developing myopia. Conversely, higher frequency of outdoor exercise, maintaining proper posture during reading and writing, greater distance from eyes to screen, and longer sleep duration were associated with lower odds. Additionally, female gender, older age, urban residence, and parental history of myopia increased the risk. The high prevalence of myopia among adolescents in Shandong Province was influenced by a combination of demographic, behavioral, and environmental factors. The study highlighted the importance of lifestyle modifications, such as increasing outdoor activities and maintaining proper visual habits, limiting the duration of screen exposure and homework sessions, and extending sleep duration, to mitigate the risk of developing myopia. These findings underscored the need for targeted public health interventions and educational campaigns to address this significant public health issue.