In this paper, the resonance frequency sensitivity of the first four bending modes of an atomic force microscope with rectangular cross section to the changes of sample stiffness in liquid environment has been investigated. The cantilever has been modeled by employing the Timoshenko beam model, and the hydrodynamic and the interaction forces between cantilever tip and sample have been included in the simulations. A comparison has been made between the frequency sensitivities of higher modes in air and liquid environments. The obtained results indicate that a greater sensitivity exists in air medium than in liquid medium. Moreover, since the frequency response of the atomic force microscope is influenced by the environment in which it is used, the effects of the fluid's mechanical parameters on the sensitivity of higher modes have been explored. The findings indicate the major impact of density and minor impact of viscosity on the frequency sensitivity of higher modes. Next, the frequency sensitivities of higher modes in various liquids have been studied and compared with one another in order to provide a guideline for the users, so that they can excite the best mode to achieve the highest contrast with regards to sample stiffness and the operating environment. Finally, the effect of angle between cantilever and sample and the probe position on the sensitivity of higher modes in water has been investigated. With the increase of angle, the higher modes become sensitive for softer samples at a faster rate; and as the tip are moved away from the cantilever end, the sensitivity of the higher modes delays.