Coastal areas are key regions between the continent and open ocean, where land-derived chemical species transported by rivers and groundwater mix with seawater. These coastal areas are also highly productive but are particularly vulnerable to human activities. The central northern Gulf of Mexico (nGoM) provides a particularly interesting region to study the land-ocean interface. While seemingly dominated by the Mississippi River Delta, the nGoM nonetheless has several physiographic regions including: the narrow shelf area near the Delta, which is dominated by Mississippi River outflow; the broad, shallow Louisiana Shelf wherein outflow of the Atchafalaya River is prevalent; and the less-studied Mississippi Bight (east of the Delta) where other fluvial sources are potentially important. Indeed, measurement of the oxygen isotope composition of nGoM surface waters allows us to see the different fresh water influences in this region with the surprising result that Mississippi River water typically plays only a minor role in the Mississippi Bight. Trace element distributions provide additional constraints on processes in the nGoM. Bottom water distributions of dissolved Ba, Mn, and V, in particular, reveal interactions with the sediments with inputs of Ba and Mn removal of V associated with hypoxia. Dissolved V can also show bottom water inputs, suggesting a seasonal change in the nature of the subsurface chemistry. Finally, in the Mississippi Bight, with naturally occurring radium isotopes, we observe a significant influence of submarine groundwater discharge (SGD) in bottom waters that is also correlated with hypoxic conditions. This relationship suggests that “bottom-up” influence of reduced substances on oxygen consumption can be an important contributor to hypoxia.