Bottom trawling has many impacts on marine ecosystems, including seafood stock impoverishment, benthos mortality, and sediment resuspension. Historical records of this fishing practice date back to the mid-1300s. Trawling became a widespread practice in the late 19th century, and it is now progressively expanding to greater depths, with the concerns about its sustainability that emerged during the first half of the 20th century now increasing. We show here that compared with untrawled areas, chronically trawled sediments along the continental slope of the north-western Mediterranean Sea are characterized by significant decreases in organic matter content (up to 52%), slower organic carbon turnover (ca. 37%), and reduced meiofauna abundance (80%), biodiversity (50%), and nematode species richness (25%). We estimate that the organic carbon removed daily by trawling in the region under scrutiny represents as much as 60–100% of the input flux. We anticipate that such an impact is causing the degradation of deep-sea sedimentary habitats and an infaunal depauperation. With deep-sea trawling currently conducted along most continental margins, we conclude that trawling represents a major threat to the deep seafloor ecosystem at the global scale. Significance Deep-sea ecosystem processes play a key role in global functioning of the planet. These functions are largely dependent upon deep-sea biodiversity. Industrial fisheries, after the depletion of fish stocks and destruction of the marine habitats on continental shelves, are now rapidly moving deeper into the ocean interior. We show here that bottom trawling along continental slopes has a major impact on deep-sea sedimentary ecosystems, causing their degradation and infaunal depauperation. Deep-sea fisheries, indeed, cause the collapse of benthic biodiversity and ecosystem functions, with potential consequences on the biogeochemical cycles. These findings support the claim of immediate actions for a sustainable management of fisheries in deep-sea environments.