A novel strategy is demonstrated to obtain polyamides with finely tunable structure using the Ugi four-component reaction (Ugi-4CR). By the use of two bifunctional and two monofiinctional components, six different combinations for the synthesis of polyamides via the Ugi-4CR are possible and were investigated in detail within this contribution. In contrast to conventional polyamide synthesis, this approach proceeds under very mild reaction conditions and without the use of a catalyst in a one-pot reaction. General applicability is shown by variation of the components, leading to finely tuned macromolecular structures (i.e., side groups and repeat units can be engineered). Finally, a facile introduction of clickable alkyne moieties is demonstrated, which was used for post-polymerization modification in an azide-alkyne cycloaddition, in order to demonstrate the high versatility of this approach.