The microstructure evolution of Al-Cu-Li-Mn-Zr-Ti alloy during homogenization was investigated by optical microscopy (OM), scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDX), and differential scanning calorimeter (DSC) methods. The results show that severe dendritic segregation exists in the experimental alloy ingot. Numerous eutectic phases can be observed in the grain boundary, and the distribution of the main elements along the interdendritic region varies periodically. The main secondary phase is Al2Cu. The overburnt temperature of the alloy is 520 °C. The second phases are gradually dissolved into the matrix, and the grain boundaries become spare and thin during homogenization with increasing temperature or prolonging holding time. Homogenization can be described by a constitutive equation in exponential function. The suitable homogenization treatment for the alloy is (510 °C, 18 h), which agrees well with the results of homogenization kinetic analysis.