Extreme hybrid growth is common in mammals, indicating that disruption of early development may play an important role in mammalian speciation. Hybrid growth effects often follow a parent-of-origin dependent pattern where reciprocal hybrids differ in size and are either larger or smaller than the parental species. Disruption of genomic imprinting, the parent-specific epigenetic silencing (imprinting) of one allele, has been linked to growth effects underlying diverse human diseases and has been hypothesized to be the predominant cause of abnormal hybrid growth. This hypothesis predicts that loss of imprinting in hybrid placentas should result in parent-of-origin dosage imbalances between paternally expressed growth factors and maternally expressed repressors. We have combined transcriptomic and quantitative genetic experiments to dissect the regulatory underpinnings of extreme parent-of-origin hybrid overgrowth between two species of dwarf hamsters. First, we tested for disrupted placental gene expression in overgrown hybrid placentas. We observed extensive transgressive expression of growth-related genes and bi-allelic expression of several paternally imprinted genes generally associated with growth repression. Surprisingly, the apparent disruption of paternal imprinting was also associated with severely reduced expression levels. These patterns are contrary to the predictions of the loss of imprinting model and suggest that misexpression of dosage sensitive genes in hybrids is caused by other mechanisms in this system. Next, we performed a backcross and identified the X chromosome as the major maternal factor explaining hybrid placental overgrowth. Expression analyses on large and normal backcross placentas revealed substantial autosomal misexpression but normal imprinted expression of the X chromosome. These results indicate that X-linked genetic incompatibilities are not caused by chromosome-wide de-regulation but may be involved in epistatic interactions that lead to the disruption of autosomal imprinting. Collectively, our results support a central role for both disrupted epigenetic processes and the X chromosome in the evolution of extreme hybrid growth in mammals.