This thesis deals with the thermo-mechanical simulation of laser beam welding for aluminum-copper joints, using the finite element method. Main focus lies on computational approaches to model the temperature field distribution and to describe the structural material behavior of pure aluminum and copper. First of all the material behavior for the corresponding base materials is validated. This is followed by approaches for efficient heat source calibration and material modeling of heterogeneous aluminum-copper joints. Numerical computations are supported by experimental studies. To compute welding distortions, two different approaches are presented. Initially a generic elasto-plastic material model formulation is analyzed. Material parameters for the generic approach are calibrated based on tensile shear testing of overlap joint specimens. Next a novel approach is introduced with respect to common state of the art thermo-mechanical welding simulation, which tries to estimate effective material properties. The basic idea of this concept is to model the material behavior by incorporating all relevant microscale details. The macroscopic or effective material response is obtained by homogenization, based on representative volume elements or virtual microstructures. These representative volume elements include all necessary micro-heterogeneities and different microstructures. On the example of mild mixing aluminum-copper lap joint weldings, multiple volume elements are reconstructed from realistic microstructures at various positions within the weld seam. Derived effective material properties are transferred to thermo-mechanical welding simulation and have been compared to experimental results.