Oral squamous cell carcinoma (OSCC) is a serious public health problem in various Asian countries, including Sri Lanka, and a combination of cultural practices, lifestyle factors, and genetic predispositions influences the incidence of these cancers. The examination of the connection between exposure to heavy metals and the probability of developing oral potentially malignant disorders (OPMD) and OSCC has been limited in its scope, and the overall consequences of such exposure remain largely unknown. This study aims to clarify the link between serum levels of heavy metals and the risk of OSCC and OPMD. The concentrations of seven heavy metals—namely, arsenic (As), cadmium (Cd), chromium (Cr), cobalt (Co), copper (Cu), lead (Pb), and zinc (Zn)—were analyzed in serum samples from 60 cases and 15 controls in the Sri Lankan cohort. The Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) was used for the analysis. Subsequently, the data underwent statistical evaluation via the Kruskal–Wallis H test, using the Statistical Package for Social Sciences (SPSS) version 28 software, with a confidence interval set at 95%. A p-value less than 0.05 was considered statistically significant. The cohort consisted of 48 men and 27 women, with 15 patients each diagnosed with OSCC, OSF, OLK, and OLP, and 15 healthy controls. The study used the Kruskal–Wallis Test to compare metal concentrations across groups, finding significant differences for all metals except As and Pb. Significant associations were observed between age, past medical history, drug history, gender, smoking, alcohol consumption, and betel chewing. The Spearman Correlation test showed significant correlations between the concentrations of Cr, Co, Cu, As, and Zn and the presence of cancer/precancer conditions. The study’s findings suggest that heavy metal contamination may be linked to the development of OSCC and precancerous conditions. When comparing OSCC and OPMD cases with controls, the serum concentrations of As and Pb did not differ significantly. However, Cd, Cr, Co, Cu, and Zn exhibited significantly higher concentrations among cases compared to controls (p < 0.05). This study observed significant variations in the levels of these five heavy metals among cancerous (OSCC), premalignant (OPMD), and healthy tissues, suggesting a potential role in the progression of malignancies. These findings underscore the importance of environmental pollution in this specific context.