We employed the XRD-CT technique to study, for the first time, the evolving solid-state chemistry of a commercial cylindrical 18650 Li-ion battery under operating conditions. More specifically, we applied this high resolution diffraction imaging technique to investigate both the cathode and anode as well as the multiple heterogeneities in the lithium distribution within each electrode and in the cell cross section. The very large (ca. 4,000,000) and rich diffraction (13 phases identified) data obtained through diffraction imaging were analysed with the state-of-the-art Parameter Quantification neural network (PQ-Net) which allowed for semi-automated and ultra-fast data analysis resolving the evolution of the complex chemistry of this multi-component system. The lithium distribution at the anode side was observed indirectly through the distribution of various crystalline LixC phases while the lithium distribution at the cathode side was observed from the distribution of the lattice parameters of the hexagonal LiNi0.8Co0.15Al0.5O2 (NCA) phase. Our investigation revealed the presence of three different regions in the anode affecting its ability to interact with lithium. The inactive-to-lithiation region is primarily a result of the cell geometry, as the aluminum tab and separator were identified in its close proximity; in both cases there is a lack of cathode material (i.e. cathode tape) opposite the respective anode. While the presence of a delayed-lithiation region at lower voltages (< 4.0 V) cannot be explained by the cell geometry, its occurrence was seen to negatively affect the distribution of lithium at the cathode side in the layers adjacent to it at discharged states. Importantly, although the battery was not investigated in situ during discharge (de-lithation), the ex situ XRD-CT measurements of the discharged cell indicated that the three regions (i.e. uniform/homogenous lithiation, delayed lithiation and inactive-tolithiation regions) behave in a similar manner during cell discharging (de-lithiation). It should be emphasized that it was the combination of in situ measurements and XRD-CT that allowed us to identify this key finding; it is possible that the battery degradation (capacity fade and/or cell failure) will initialise in this region. This could allow for early-on identification of potential regions where cell degradation will develop before there is an indication through measurements of macroscopic properties (e.g. capacity fade from cycling stability measurements). Further to this, the presence of the Al tab affected the distribution of lithium in the cathode material being in direct contact with it, preventing lithium insertion during discharging and trapping the lithium during charging. This research highlights the impact of cell geometry on the initial capacity loss which is indicated to be primarily driven by the heterogeneities at the anode side. Finally, it should be noted that XRD-CT has the potential to be applied for a wide variety of different experiments related to battery degradation mechanisms, such as in situ/ operando abusing testing to capture internal temperature gradients through the crystallographic behaviour of the anode/cathode as well as ex situ measurements to investigate active layer delamination and local corrosion of spent samples.