Significance Research on the chemical origin of life comprises one of the most exciting topics in contemporary science. Prebiotic chemistry provided evidence that precursors of both nucleic acids and proteins might be formed in the prebiotic environment. Yet, studies on nonenzymatic replication—a central mechanism driving chemical evolution—focused largely on each class of these molecules separately. This paper reveals a successful attempt to replicate simple nucleopeptide chimeras. Most importantly, different mechanisms control the replication of complementary chimeras, leading to a clear selection of one over the other. We propose that related processes may have led to the emergence of the first functional nucleic-acid–peptide assemblies, which further developed into biological assemblies such as the ribosomes and viruses.