Reversible modulation of upconversion luminescence induced by the external field stimuli exhibits potential applications in various fields, such as photoswitches, optical sensing, and optical memory devices. Herein, a new MoO3:Yb3+,Er3+ thermochromic phosphor was synthesized via a high-temperature solid-state method, and the reversible color modification of the MoO3:Yb3+,Er3+ phosphor was obtained by alternating the sintering conditions either in a reducing atmosphere or in air. The color of the MoO3:Yb3+,Er3+ phosphor changed from light-yellow to blue under sintering in the reducing atmosphere and returned back after sintering again in air. The influence of reversible thermochromism on the upconversion luminescence of MoO3:Yb3+,Er3+ phosphor was investigated. The MoO3:Yb3+,Er3+ phosphor prepared in air exhibited visible upconversion luminescence, while the MoO3:Yb3+,Er3+ phosphor has no upconversion luminescence after sintering in the reducing atmosphere. This up-conversion luminescence modulation shows excellent reproducibility after several cycles. The thermochromic MoO3:Yb3+,Er3+ phosphor with reversible modulated upconversion luminescence shows great potential for practical applications in optical switches and optoelectronic multifunctional devices.