The genome of Streptomyces coelicolor encodes hundreds of putative regulatory proteins, most of which are of unknown function, including SCO5351. In this study, we determined that deletion of sco5351 largely abrogates production of actinorhodin (ACT) and reduces production of the calcium-dependent antibiotic (CDA). Comprehensive transcriptional analyses indicated that transcription of genes of the ACT pathway, including the pathway-specific regulator actII-orf4 and those involved in the building of the chemical compound, was markedly lower in Δsco5351 in the late growth phase. However, transcription of genes in the CDA cluster was notably reduced in Δsco5351 only in the early growth phase, suggesting that SCO5351 has a regulatory role throughout growth. Similar to the observations with Δsco5351, ACT production was blocked by mutagenesis of three conserved amino acids potentially involved in dimerization of SCO5351, indicating that protein dimerization is critical to the function of SCO5351. In addition, disruption of sco5351 delayed the formation of aerial mycelium and spores under the conditions tested and, consistent with this, transcription of developmental genes associated with spore formation was reduced in Δsco5351, implying that SCO5351 is involved in developmental control. Our findings reveal SCO5351 as a pleiotropic regulator with roles in both secondary metabolism and morphological development in S. coelicolor.