Cerro Negro volcano is a young basaltic cinder cone which is part of the Nicaraguan volcanic arc. Eruptive activity at Cerro Negro is characterized by explosive strombolian to subplinian eruptions driven by volatile-rich basaltic magma ascending rapidly from various crustal depths (>15 to 6 km) resulting in the onset of precursory activity only ∼30 min before an eruption. In this paper, we present a comprehensive degassing characterization of the volcano over a 4-year period aimed at improving our understanding of the magmatic plumbing network and its relationship with regional tectonics. A total of 124 individual soil gas samples were collected between 2010 and 2013 and analyzed for stable carbon isotopes (δ13C) from CO2. High temperature fumaroles were sampled for δ18O, δD, and 3He/4He isotope analysis, and major degassing zones were mapped using soil CO2 flux measurements. Gases at Cerro Negro are characterized by a strong 3He/4He mantle signature (6.3 to 7.3 RA), magmatic δ13C ratios (−2.3 to −3.0 ‰), meteoric δ18O and δD ratios, and stable CO2 fluxes (31 t d−1). The lack of δ13C fractionation and an increase in the relative mantle component from 2002 to 2012 suggest that the volatile flux at Cerro Negro originates from the mantle and ascends to the surface via a series of crustal fractures that act as permeable conduits. Despite the lack of new eruptions, the hydrothermal system of Cerro Negro continues to evolve due to seasonal inputs of meteoric water, slope failures that expose and bury sites of active degassing, and bursts of regional seismicity that have the potential to open up new conduits for gas release as well as magma. Continuing geophysical and geochemical monitoring of the main edifice and the recently formed south zone is essential, as the volcano remains overdue to erupt.