A chemical investigation of <i>Streptomyces</i> sp. SCSIO 40069 resulted in the isolation of a series of aromatic polyketides with rare skeletons, including five new compounds RM18c-RM18g (<b>1</b>-<b>5</b>) and three known ones (<b>6</b>-<b>8</b>). Their structures and absolute configurations were determined by diverse methods, including HRMS and NMR spectra, chemical reaction, Snatzke's method, quantum mechanical-nuclear magnetic resonance (QM-NMR), and X-ray crystallographic analysis. Compounds <b>1</b>, <b>2</b>, <b>4b</b>, and <b>8</b> displayed moderate or weak antibacterial activities.