Hydrocarbon seepage is widespread distributed at the southern Gulf of Mexico. During several research cruises in 2003, 2006, and 2015 (SO174, M67/, and M114) we used multidisciplinary approaches, including multi-beam mapping and visual seafloor observations with different underwater vehicles to study the extent and character of complex hydrocarbon seepage in the Bay of Campeche, southern Gulf of Mexico. Our observations showed that seafloor asphalt deposits occur at numerous knolls and ridges in water depths from 1230 to 3150 m. These striking seafloor elevations are formed by diapirs of Jurassic salt deposit associated by hydrocarbon accumulations. The deeper sites like Chapopopte and Mictlan knolls were characterized by asphalt deposits accompanied by extrusion of liquid, and very heavy oil in form of whips or sheets, and in most places by gas emissions, and the presence of gas hydrates (Tsanyao Yang, Mictlan, and Chapopote knolls). Molecular and stable carbon isotopic compositions of gaseous hydrocarbons suggest their primarily thermogenic origin. Relatively fresh solidified asphalt structures were settled by bacterial mats and vestimentiferan tube worms growing through cracks and from under the edges of pavement. The gas hydrates at Tsanyao Yang and Mictlan knolls were covered by a 5-to-10 cm-thick reaction zone composed of authigenic carbonates, detritus, and microbial mats, and were densely colonized by 1–2 m long tube worms, bivalves, snails, and shrimps. The extent of all discovered seepage structure areas indicates that emission of complex hydrocarbons is a widespread, thus important feature of the southern Gulf of Mexico.