Acute effects of individual and complex mixtures of polycyclic aromatic hydrocarbons (PAHs) are well documented in vertebrate species. Hypoxia in fish reduces metabolic rate and reproduction. However, less is known about the later life consequences stemming from early-life exposure to PAHs or hypoxia, particularly their co-exposure. To address this, medaka (Oryzias latipes) embryos were exposed to a complex PAH mixture sediment extract from the Elizabeth River, VA (ERSE) at concentrations of 0.1, 0.5, or 1.0% or to one of three different hypoxia scenarios: continuous, nocturnal, or late stage embryogenesis hypoxia. Co-exposures with 0.1% ERSE and each of the hypoxia scenarios were conducted. Results included decreased survival with ERSE, hatching delays with hypoxia, and higher occurrences of deformities with each. The continuous hypoxia scenario caused the most significant changes in all endpoints. These early-life exposures altered later-life growth, impaired reproductive capacity, and reduced the quality of their offspring. ERSE alone resulted in a female-biased sex ratio while continuous or nocturnal hypoxia produced significantly greater numbers of males; and co-exposure produced an equal sex ratio. Exposure to a PAH mixture and hypoxia during early life stages has meaningful later-life and next generational consequences.