The current study describes a detailed steady-state analysis and transient operation of a multi-effect desalination plant with a thermal vapor compressor unit (MED-TVC). The model developed is based on solving the basic conservation equations of mass, energy, and salt. It can predict steady-state operation and transient behavior when the plant is subject to abrupt changes in the main input parameters including motive steam flow rate (m(ms)), cooling seawater flow rate (m(cw)) and cooling seawater temperature (T-cw). These sudden changes simulate the conditions a MED-TVC plant may be exposed to. Both the steady-state and dynamic aspects of the model are validated against published experimental data. Monitoring the variation of four state variables (vapor temperature, brine level, brine and vapor flow rates) in each effect shows that disturbances in the motive steam flow rate and the cooling seawater temperature have a significant effect on the plant performance. On the other hand, the disturbance in the cooling seawater mass flow rate has only a moderate effect. For all applied disturbances, the change in the brine level is the slowest compared to the changes in vapor temperature, and brine and vapor flow rates. Furthermore, the effect of changing seawater salinity shows a slight effect on the total distillate production and the specific heat transfer area.