Orthorhombic β-LiScGe2O6 single crystals were compressed hydrostatically up to 10.35 GPa using a diamond anvil cell and investigated in situ by means of X-ray diffraction and Raman spectroscopy. Crystal-structure investigations at ambient conditions and at high pressure show a structural transition from an orthopyroxene-type Pbca structure (a ≈ 18.43 Å, b ≈ 8.85 Å, and c ≈ 5.34 Å at 8.6 ± 0.1 GPa) to a postorthopyroxene type P21/c structure of the new dense γ-LiScGe2O6 (a ≈ 18.62 Å, b ≈ 8.85 Å, c ≈ 5.20 Å, and β ≈ 93.1° at 9.5 ± 0.1 GPa). The structure refinements reveal displacive shifts of O atoms associated with a rotation of every other tetrahedral-chain unit from the O- to S-type position similar to the postorthopyroxene-type MgSiO3. As a consequence of the oxygen displacement, the coordination number of Li atoms is changing from [5 + 1] to a proper 6-fold coordination. The transition around Pc = 9.0 ± 0.1 GPa is associated with a volume discontinuity of ΔV = -1.6%. This orthopyroxene (OEn-Pbca) to postorthopyroxene (pOEn-P21/c) transition is the second example of this type of transformation. Precise lattice parameters have been determined during isothermal compression. The fit of the unit-cell volumes of β-LiScGe2O6, using a third-order Birch-Murnaghan equation of state, yields V0 = 943.63 ± 0.11 Å3, K0 = 89.8 ± 0.6 GPa, and dK/dP = 4.75 ± 0.18 as parameters. Evaluation of the data points beyond the critical transition pressure using a second-order Birch-Murnaghan equation suggests V0 = 940.6 ± 4.4 Å3 and K0 = 82.4 ± 4.8 GPa. A series of high-pressure Raman spectra confirm the symmetry-related structural transition, with band positions shifting in a noncontinuous manner, thus confirming the proposed first-order transition.