Variation of the sound velocities, elastic constants, and compressibility of a natural magnetite crystal were determined using gigahertz ultrasonic interferometry and single-crystal X-ray diffraction to 8.7 GPa. At ambient pressure, the elastic constants are (in GPa): c11 = 260.5(1.0), c12 = 148.3(3.0), and c44 = 63.3(1.5). While c11 and c12 have similar positive pressure derivatives of 5.14(13) and 5.39(10), respectively, the c44 elastic constant exhibits mode-softening over this pressure range, with dc44/dP = 0.13(4), calculated from the pressure dependence of the  shear velocity. The adiabatic bulk modulus (K0S) is 185.7(3.0) GPa, with KS = 5.1(1), and the shear modulus (G0) is 60.3(3.0) GPa, with G′ = −0.1(1). The bulk modulus and its pressure derivative obtained dynamically are consistent with the isothermal equation of state, measured on the same sample by single-crystal X-ray diffraction, yielding K0T = 180.0(1.0) and KT′ = 5.2(4). Pressure-induced shear-mode softening in magnetite is most likely related to magnetoelastic coupling and the first-order phase transition to an orthorhombic structure above 21 GPa.