Background: Periodontitis is a chronic inflammatory disease characterized by progressive destruction of the tooth-supporting tissues and may substantially impair oral health-related quality of life (OHRQoL). Although the clinical consequences of periodontitis are well documented, the extent to which disease severity is associated with patient-reported outcomes remains insufficiently understood. This study aimed to evaluate the association between periodontitis severity and OHRQoL and to examine sociodemographic, behavioral, and systemic factors associated with poorer OHRQoL. Methods: A cross-sectional analytical study was conducted among 136 adult patients diagnosed with stage II or stage IV periodontitis at the Periodontology Clinic of Universidad Tecnológica de México (UNITEC). OHRQoL was assessed using the Oral Health Impact Profile for Periodontal Disease (OHIP-14-PD). Sociodemographic characteristics, smoking status, and diabetes mellitus were recorded using a structured questionnaire. Periodontal status was determined through standardized clinical and radiographic examinations. The internal consistency of the OHIP-14-PD was evaluated using Cronbach’s alpha coefficient. Bivariate analyses were performed using non-parametric tests. An exploratory, partially adjusted multivariable linear regression model including sex, marital status, diabetes mellitus, and periodontitis stage was also performed. Results: Stage IV periodontitis was more prevalent than stage II periodontitis (55% vs. 45%). The mean OHIP-14-PD score was 24.9 ± 13.7, and the instrument demonstrated excellent internal consistency (Cronbach’s α = 0.89). Patients with stage IV periodontitis had significantly higher OHIP-14-PD scores than those with stage II disease (30.1 ± 12.4 vs. 18.6 ± 12.6; p < 0.001), indicating poorer OHRQoL. In the bivariate analyses, poorer OHRQoL was also observed among current smokers, participants with diabetes mellitus, those with lower educational attainment, and those with lower socioeconomic status (p < 0.05). In the exploratory partially adjusted model, male sex (β = 4.2; 95% CI: 0.1–8.2; p = 0.042), diabetes mellitus (β = 6.5; 95% CI: 2.1–10.9; p = 0.004), and stage IV periodontitis (β = 4.6; 95% CI: 0.4–8.7; p = 0.031) were associated with higher OHIP-14-PD scores. Conclusions: In this single-center cross-sectional sample, patients with stage IV periodontitis reported higher OHIP-14-PD scores than those with stage II periodontitis. These findings indicate an association within the studied clinical population and should not be interpreted as evidence of a causal effect or as directly generalizable to broader populations. Larger multicenter longitudinal studies including patients across all periodontitis stages are required to confirm the magnitude and external validity of this association.