We present a coupled left atrium‐mitral valve model based on computed tomography scans with fibre‐reinforced hyperelastic materials. Fluid‐structure interaction is realised by using an immersed boundary‐finite element framework. Effects of pathological conditions, eg, mitral valve regurgitation and atrial fibrillation, and geometric and structural variations, namely, uniform vs non‐uniform atrial wall thickness and rule‐based vs atlas‐based fibre architectures, on the system are investigated. We show that in the case of atrial fibrillation, pulmonary venous flow reversal at late diastole disappears, and the filling waves at the left atrial appendage orifice during systole have reduced magnitude. In the case of mitral regurgitation, a higher atrial pressure and disturbed flows are seen, especially during systole, when a large regurgitant jet can be found with the suppressed pulmonary venous flow. We also show that both the rule‐based and atlas‐based fibre defining methods lead to similar flow fields and atrial wall deformations. However, the changes in wall thickness from non‐uniform to uniform tend to underestimate the atrial deformation. Using a uniform but thickened wall also lowers the overall strain level. The flow velocity within the left atrial appendage, which is important in terms of appendage thrombosis, increases with the thickness of the left atrial wall. Energy analysis shows that the kinetic and dissipation energies of the flow within the left atrium are altered differently by atrial fibrillation and mitral valve regurgitation, providing a useful indication of the atrial performance in pathological situations.