High harmonic generation (HHG) takes place in all phases of matter. In gaseous atomic and molecular media, it has been extensively studied and is very well understood. In solids, research is ongoing, but a consensus is forming for the dominant microscopic HHG mechanisms. In liquids, on the other hand, no established theory yet exists, and approaches developed for gases and solids are generally inapplicable, hindering our current understanding. We develop here a powerful and reliable ab initio cluster-based approach for describing the nonlinear interactions between isotropic bulk liquids and intense laser pulses. The scheme is based on time-dependent density functional theory and utilizes several approximations that make it feasible yet accurate in realistic systems. We demonstrate our approach with HHG calculations in water, ammonia, and methane liquids and compare the characteristic response of polar and nonpolar liquids. We identify unique features in the HHG spectra of liquid methane that could be utilized for ultrafast spectroscopy of its chemical and physical properties, including a structural minimum at 15-17 eV that is associated solely with the liquid phase. Our results pave the way to accessible calculations of HHG in liquids and illustrate the unique nonlinear nature of liquid systems.