Tuberculosis (TB) ranks as the leading cause of death from a single infectious agent (ranking more lethal than HIV/AIDS) over the course of the past decade. More concerning is that reports of multi-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of TB have been dramatically increasing. It continues to become ever more clear that novel anti-TB drugs with improved efficacies and reduced toxicities are urgently needed. We report here the discovery of 12 new ilamycin analogues, ilamycins G-R (<b>1</b>-<b>12</b>), bearing various nonproteinogenic amino acids, along with ilamycins E<sub>1</sub> (<b>13</b>) and F (<b>14</b>), from a 200 L scale culture of the marine-derived mutant actinomycete <i>Streptomyces atratus</i> SCSIO ZH16 Δ<i>ilaR</i>. Importantly, bioassays against <i>Mycobacterium tuberculosis</i> H37Rv revealed that all 12 new agents displayed antitubercular activities with MIC values ranging from 0.0096 to 10 μM. The structures of <b>1</b>-<b>12</b> were elucidated on the basis of HRESIMS, 1D and 2D NMR, and X-ray single-crystal diffraction studies. In addition, compound <b>10</b> was found to be moderately cytotoxic against a panel of tumor human cell lines. From these data we can formulate tentative structure-activity relationships for the antitubercular and antitumor activities of the ilamycins.