We report on a detailed experimental investigation of the equation of state (EoS) of the three-dimensional Fermi-Hubbard model (FHM) in its generalized SUðNÞ-symmetric form, using a degenerate ytterbium gas in an optical lattice. In its more common spin-1=2 form, the FHM is a central model of condensed-matter physics. The generalization to N > 2 was first used to describe multi-orbital materials and is expected to exhibit novel many-body phases in a complex phase diagram. By realizing and locally probing the SUðNÞ FHM with ultracold atoms, we obtain model-free access to thermodynamic quantities. The measurement of the EoS and the local compressibility allows us to characterize the crossover from a compressible metal to an incompressible Mott insulator. We reach specific entropies above Néel order but below that of uncorrelated spins. Having access to the EoS of such a system represents an important step towards probing predicted novel SUðNÞ phases. Strongly correlated fermionic many-body systems play a fundamental role in modern condensed-matter physics. A central model for these systems is the Fermi-Hubbard model (FHM), originally developed for describing interacting electrons in a crystal. It explains a wide range of observed phenomena such as metal-to-insulator transitions and magnetic order, and is believed to capture the essential physics of d-wave superfluidity in high-temperature superconductors [1,2]. The generalized SUðNÞ-symmetric version of the FHM was originally studied in the context of transition-metal oxides with effective higher spin [3].Although the FHM has been the object of a large number of studies in past decades, reaching a complete understanding has remained an elusive task, even for the spin-1=2 case. For strong repulsive interactions, the SU(2) FHM is known to give rise to a paramagnetic Mott insulator, where antiferromagnetic order emerges below the Néel temperature. Already in this limit of strong interactions and low temperature, the SUðN > 2Þ case has been predicted to exhibit a rich phase diagram with a variety of different correlated states [4][5][6][7][8][9][10][11][12][13].The development of experimental implementations of the three-dimensional (3D) FHM with ultracold atoms has provided a new approach for advancing our understanding of strongly correlated fermions in lattices [14]. The recent realization of degenerate gases of strontium and ytterbium [15,16], in combination with optical lattices, allows us to extend this beyond the conventional spin-1=2 FHM and to access the more general SUðN > 2Þ symmetry. Numerical calculations in this regime are, so far, mostly limited to T ¼ 0, low dimensions, or approximated correlations. Accurate predictions of thermodynamic quantities are even harder to obtain than for the SU(2) case, as most algorithms struggle with larger N due to the unfavorable scaling of the Hilbert space. Probing the thermodynamics of such systems, implemented with ultracold atoms, provides access to this challenging regime and allows for the testing of novel algorit...