Despite ongoing efforts, recent data indicate that periodontal conditions remain widespread among adolescents. This highlights the continued need for school-based strategies that encourage effective oral hygiene routines. Establishing baseline information on adolescents’ hygiene behaviors and how these behaviors relate to their oral-health-related quality of life is essential for planning targeted interventions. Because oral health-related quality of life reflects the extent to which oral conditions interfere with daily functioning, it offers a comprehensive way to involve individuals in decisions about their oral care and their willingness to maintain preventive habits. To determine how oral hygiene behaviors influence the oral-health-related quality of life of adolescents. A cross-sectional survey was administered to 1,800 adolescents aged 14–18 years enrolled in 36 Senior Secondary Schools across metropolitan Ibadan, Nigeria. Information was obtained using a self-completed questionnaire covering sociodemographic details, oral hygiene behaviors, and OHRQoL assessed with COHIP-SF19. Analyses were conducted with SPSS version 25, adopting a significance level of p < 5%. Participants had a mean age of 15.16 (±1.16) years. A total of 1,094 (60.3%) brushed their teeth at least twice daily, 126 (7.0%) brushed after meals, and 1,519 (84.4%) replaced their tooth-cleaning materials every three months or sooner. Additionally, 1,215 (67.5%) spent three minutes or longer brushing. Only 238 (13.2%) practiced interdental cleaning and 137 (7.6%) used dental floss. Reported OHRQoL scores ranged from 9–76, with 1,612 (93.5%) experiencing at least one negative impact. Brushing at least twice daily was associated with better OHRQoL (OR = 1.6, 95% CI = 1.1–2.4, p = 0.025), while those who did not clean interdentally were more likely to report better OHRQoL (OR = 2.8, 95% CI = 1.2–6.5, p = 0.014). Overall, oral hygiene behaviors were below ideal standards. Adolescents who brushed twice or more per day reported fewer impacts on OHRQoL, whereas those who performed interdental cleaning showed greater impacts than their peers.