The objective of this study was to perform a long-term modeling of the sedimentation rate of one of the largest reservoirs in the Republic of Macedonia, i.e., the Tikvesh reservoir. The developed mathematical model should serve for detailed analysis of the sedimentation rate in the reservoir over time, and if the obtained results are acceptable, it should be further developed and used in defining practices of sustainable management of the reservoir in future. For this purpose, a widely applied, semi-distributed, and process-based watershed-scale model SWAT was used. Using SWAT, the production of sediments in the watershed as well as their transport through the river network was modeled. Based on the empirically estimated reservoir trap efficiency as well as bulk density of the settled material, volumetric sediment budgeting was done, whereby the temporal distribution of the reservoir sedimentation rate was defined. The obtained results were compared with the information from several bathymetric surveys of the reservoir whereat a satisfactory match was found. The model was generated for the period extending from 1969, when the reservoir was put into operation, to 2016, when the last bathymetric survey was conducted. The period between 1969 and 1985 was used for calibration of the model, while the period from 1986 to 1991 was used for its validation. Forecast referring to the change of the deposited quantities of sediments in the reservoir was made for the period from 1992 to 2016. In the absence of reliable data from measurements done in this period, climate data generation and consequently watershed sedimentation yield estimation by using the WXGEN-weather generator-were conducted. The obtained results point to variable sedimentation rate of the reservoir in different periods, depending on the variability of the weather conditions within the watershed. The average sedimentation rate of the reservoir in the analyzed period 1969-2016 at an annual level is 0.02-1.28% of the initial volume, which is around the estimated world average amounting to 0.5-1%.