The natural occurrence of clinohumite in metabasalts and hydrothermally altered peridotites provides a source of water‐rich minerals in subducted slabs, making knowledge of their phase relations and crystal chemistry under high pressure‐temperature (P‐T) conditions important for understating volatile recycling and geodynamic process in the Earth's mantle. Here we present a synchrotron‐based, single‐crystal X‐ray diffraction study on two natural Ti‐bearing clinohumites up to ~28 GPa and 750 K in order to simulate conditions within subducted slabs. No phase transition occurs in clinohumite over this P‐T range. Pressure‐volume relationships of both compositions at room temperature were fitted to a third‐order Birch‐Murnaghan equation of state (EoS) with V0 = 650.4(3) Å3, KT0 = 141(4) GPa, and KT0′ = 4.0(6) for Ti‐poor clinohumite (0.07 Ti per formula unit, pfu) and V0 = 650.8(3) Å3, KT0 = 144(4) GPa, and KT0′ = 3.6(7) for Ti‐rich clinohumite (0.21 Ti pfu). Both clinohumites exhibit anisotropic compression with βb > βc > βa. We also refined P‐V‐T equation of state parameters using the high‐temperature Birch‐Murnaghan EoS, yielding (∂KT0/∂T)P = −0.040(10) GPa/K and αT = 5.1(6) × 10−5 K−1 for Ti‐poor clinohumite and (∂KT0/∂T)P = −0.045(11) GPa/K and αT = 5.7(6) × 10−5 K−1 for Ti‐rich clinohumite. Ti‐poor and Ti‐rich clinohumites display similar equations of state but are ~20% more incompressible than Mg‐pure clinohumite and display ~5% higher bulk sound velocity than olivine at upper mantle conditions. Our results provide constraints for modeling geodynamic process related to the subduction and transport of potentially water‐rich slabs in the mantle.