Antarctic have been suggested as an attractive source for antibiotics discovery and members of Streptomyces genus have historically been studied as natural producers of antimicrobial metabolites. Nonetheless, our knowledge on antibiotic-producing Streptomyces from Antarctic is very limited. In this study, the antimicrobial activity of organic extracts from Antarctic Streptomyces strains was evaluated by disk diffusion assays and minimum inhibitory concentration. The strain Streptomyces sp. So13.3 showed the greatest antibiotic activity (MIC = 15.6 μg/mL) against Gram-positive bacteria and growth reduction of Gram‒negative pathogens. The bioactive fraction in the crude extract was revealed by TLC‒bioautography at Rf = 0.78 with molecular weight between 148 and 624 m/z detected by LC-ESI-MS/MS. The strain So13.3 was taxonomically affiliated as Streptomyces fildesensis. Whole genome sequencing and analysis suggested a 9.47 Mb genome size with 42 predicted biosynthetic gene clusters (BGCs) and 56 putative clusters representing a 22% of total genome content. Interestingly, a large number of them (11 of 42 BGCs and 40 of 56 putative BGCs), did not show similarities with other known BGCs. Our results highlight the potential of the Antarctic Streptomyces strains as a promising source of novel antimicrobials, particularly the strain Streptomyces fildesensis So13.3, which first draft genome is reported in this work.