Mathematical models of multiple cycles for sorption-enhanced steam methane reforming and Ca-based sorbent regeneration in a fixed bed reactor are developed. Empirical correlations are used to describe steam methane reforming, the water-gas shift, and CO2 capture kinetics. The processes of multiple carbonation/calcination cycles of a Ca-based sorbent are taken into account to describe the sorption-enhanced hydrogen production process with the simultaneous removal of carbon dioxide by a Ca-based sorbent. The mathematical models are validated through comparing simulated results with experimental data. The model results qualitatively agree with experimental data. The effect of reactivity decay of dolomite, CaO/Ca12Al14O33, and limestone sorbents on sorption-enhanced hydrogen production and sorbent regeneration processes was studied through numerical simulation. The simulated results indicated that the operation time of producing high-purity hydrogen (that is defined as the time for the start of breakthrough, often referred to as prebreakthrough time) declines continuously with the increasing of cyclic number due to the sorbent activity loss; the ultimate prebreakthrough time will remain nearly constant, due to the sorbent already reaching the final residual capture capacity. The ultimate prebreakthrough time is different for different sorbents. In comparison with dolomite and limestone sorbents, CaO/Ca12Al14O33 sorbent can obtain a rather longer prebreakthrough time after a large cycle number due to its high reactivity and stability. After the reforming and CO2 removal step, the Ca-based sorbents need to be regenerated to be used for the subsequent reforming cycle, and the multiple calcination processes of Ca-based sorbents under different calcination conditions are discussed.