OBJECTIVE: Estimate the effect of age, period, and birth cohort on mortality from oral and oropharyngeal cancer in Brazil and its macro-regions. METHODS: Deaths from oral and oropharyngeal cancer from 1983 to 2017 were analyzed. The Poisson regression model was applied, using estimable functions proposed by Holford. RESULTS: From 1983 to 2017, 142,634 deaths from oral and oropharyngeal cancer were registered in Brazil, 81% among men, and the South and Southeast regions had the highest rates. The most significant period effects were observed in male mortality in the Southeast and Central-West regions for the 2003-2007 reference period. In the North, Northeast, and Central-West regions, an increased risk of mortality was observed in the most recent male cohorts. In the North region, the most significant risk identified was for men born during 1973-1977 (RR = 1.47; 95%CI 1.05-2.08); in the Northeast, for men born during 1988-1992 (RR = 2.77; 95%CI 1.66-4.63); and in the Central-West, for women born during 1973-1977 (RR = 2.01; 95%CI 1.19-3.39). In the Southeast and South regions, the most recent cohorts had lower mortality rates. The lowest risk in the Southeast region was observed in the male cohort born during 1978-1982 (RR = 0.53; 95%CI 0.45-0.62) and 1983-1987 in the South region (RR = 0.25; 95%CI 0.12-0.54). CONCLUSIONS: Age had a significant effect on mortality from oral and oropharyngeal cancer in all regions. In the North, Northeast, and Central-West regions, an increase in risk was observed in the most recent cohorts, while in the South and Southeast regions, these cohorts presented a lower risk when compared to the older cohorts.