Alcohol and cannabis are among the most commonly used recreational drugs. Of particular concern is the use of alcohol and/or cannabis by young women who become pregnant, as prenatal exposure may adversely affect the development of the fetus. Individuals exposed to alcohol prenatally may exhibit impaired spatial learning; however, the effects of prenatal cannabis on spatial learning and memory are not well understood, and even less is known of the effects of combined ethanol and cannabis exposure. Using an animal model, the present study examined the effects of prenatal alcohol and tetrahydrocannabinol (THC; the primary psychoactive agent in cannabis) exposure on spatial learning and memory. Pregnant Sprague-Dawley rats were exposed to vaporized ethanol (EtOH), THC, the combination, or vehicle control during gestation. A THC dose of 100 mg/mL and an alcohol dose of 68 mL/hour were administered from GD 5-20. One male and one female offspring from each litter were tested on the Morris water maze spatial learning task during adolescence. Prenatal THC exposure alone impaired spatial learning and memory in female, but not in male, offspring. In addition, females exposed to THC were more thigmotaxic, indicative of increased anxiety. In contrast, prenatal EtOH exposure did not significantly impair spatial memory. In addition, offspring exposed to prenatal EtOH were more thigmotaxic during the probe test, indicative of altered emotionality and/or a different search strategy. Surprisingly, performance of subjects exposed to the combination of THC and EtOH was not exacerbated compared to either drug alone and, in fact, did not differ from that of controls. Prenatal exposure to THC leads to long-lasting impairments among females, illustrating that prenatal cannabis exposure can disrupt behavioral development in a sex-dependent manner. Notably, these deficits in learning and memory were produced by low to moderate THC exposure, suggesting that even low levels of prenatal THC exposure are not safe to the fetus. Although the effects of THC were not exacerbated with co-exposure to EtOH, it is possible that higher EtOH doses may produce more severe outcomes. Collectively, these data support public health policies that focus on reducing cannabis use during pregnancy.