Transverse sensitivity of the single-axis accelerometer is one of the most important performance metrics, which has significant influence on the calibration model and accuracy. In this study, a novel model considering the transverse sensitivity is proposed to calibrate the three-axis micro-electro-mechanical systems ( MEMS) acceleration sensors. The transverse sensitivity of the model is introduced into the calibration equation as a symmetric matrix. The established calibration function includes zero deviation, scale factor error, non-orthogonal installation error and transverse sensitivity. Finally, the 12-position calibration method is utilized to collect experimental data. The maximum likelihood parameter estimation algorithm is used to solve the calibration model to achieve sensor calibration. Experimental results show that the compensation error of the calibration mathematical model is smaller in terms of mean values and variance than current calibration mathematical model. The accuracy after compensation is higher and the stability is better, which show positive effectiveness on improving the accuracy of MEMS three-axis acceleration sensor. This study has important theoretical significance and engineering application value