We studied asphalt deposits, oil seepage and gas venting during a multidisciplinary cruise in the Bay of Campeche, southern Gulf of Mexico. We conducted multibeam bathymetric mapping with an autonomous underwater vehicle and performed seafloor observations as well as sampling with a remotely operated vehicle. While previous studies concentrated on the asphalt volcano Chapopote Knoll, we confirmed that asphalt deposits at the seafloor occurred across numerous other knolls and ridges in water depths between 1230 and 3150 m; this is evidence that the outflow of heavy oil is a common component of hydrocarbon seepage of Campeche Knolls. The outflow of heavy oil either created whips or sheets floating in the water that subsequently descend and pile-up as meter high stacks at the seafloor over time or spread at the seafloor forming flows ranging from meters to tens of meters in diameter. Unlike seafloor-covering asphalts known from other continental margins, those in our study include relatively fresh material. Seafloor observations documented how chemosynthetic communities develop on the asphalts, with bacterial mats and juvenile vestimentiferan tubeworms colonizing the most recent flows. Gas bubble emissions were an additional widespread component of hydrocarbon seepage at Campeche Knolls. The hydrocarbon gas had thermogenic origins, as indicated by the composition (C1/C2-ratio: 14 to 185) and stable carbon isotopic signature of methane (δ13C-CH4: −45.1 to −49.8 ‰). Gas emissions were detected by multibeam echosounder at water depths as great as 3420 m over Tsanyao Yang Knoll. Gas emissions occurred at sites without large asphalt deposits (Tsanyao Yang Knoll) as well as through old, fragmented asphalts (Mictlan Knoll, Chapopote Knoll). The gas emissions feed gas hydrate deposits at shallow seafloor depth. Gas hydrate formed mounds that were ~ 10 m wide by several meters high in soft sediments and filled the space within fragmented asphalts. The largest gas hydrate mounds supported dense colonies of 1–2 m long tubeworms that covered areas 〉 100 m2. These tubesworms grow with their posterior tubes implanted in a 5 to 10 cm thick reaction zone composed of authigenic carbonates, detritus, and microbial mats that overlie gas hydrate layers that were at least 2 m thick in places. This association between gas hydrates and vestimentifera has been noted in gas seeps at lesser depths, but was developed to an unequaled extent in the Campeche Knolls. Previous studies have documented oil slicks on the ocean surface across many sites in the region. This study found liquid oil emissions in diverse settings. Sites with oil seepage are characterized by oil-soaked sediments, chemosynthetic fauna with associated heterotrophs, and bacterial coatings. Gas bubble emissions and oil seepage occurred independent of asphalt deposits or through old, fragmented asphalts, indicating that presently active hydrocarbon seepage overprints older asphalt deposits. Campeche Knolls are unique in several aspects including the occurrence of recent flows of heavy oil, deep-water hydrocarbon seepage, with many species that are new to science.