This study characterizes a decadal assessment of polycyclic aromatic hydrocarbons (PAHs) in the muscle tissues of mesopelagic fish species as indicators of the environmental health of the Gulf of Mexico (GoM) deep-pelagic ecosystem. Mesopelagic fishes were collected prior to the Deepwater Horizon (DWH) oil spill (2007), immediately post-spill (2010), 1 year after the spill (2011), and 5–6 years post-spill (2015–2016) to assess if the mesopelagic ecosystem was exposed to, and retained, PAH compounds from the DWH spill. Results indicated that a 7- to 10-fold increase in PAHs in fish muscle tissues occurred in 2010–2011 (4972 ± 1477 ng/g) compared to 2007 (630 ± 236 ng/g). In 2015–2016, PAH concentrations decreased close to the levels measured in 2007 samples (827 ± 138 ng/g); however, the composition of PAHs still resembles a petrogenic source similar to samples collected in 2010–2011. PAH composition in muscle samples indicated that natural sources (e.g., Mississippi River and natural seeps) or spatial variability within the GoM do not explain the temporal variability of PAHs observed from 2007 to 2016. Furthermore, analysis of different fish tissues indicated the dietary intake and maternal transfer of PAHs as the primary mechanisms for bioaccumulation in 2015–2016, explaining the elevated levels and composition of PAHs in ovarian eggs.