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Abstract The XX/XY sex chromosome system is deeply conserved in therian mammals, as is the role of Sry in testis determination, giving the impression of stasis relative to other taxa. However, the long tradition of cytogenetic studies in mammals documents sex chromosome karyotypes that break this norm in myriad ways, ranging from fusions between sex chromosomes and autosomes to Y chromosome loss. Evolutionary conflict, in the form of sexual antagonism or meiotic drive, is the primary predicted driver of sex chromosome transformation and turnover. Yet conflict-based hypotheses are less considered in mammals, perhaps because of the perceived stability of the sex chromosome system. To address this gap, we catalog and characterize all described sex chromosome variants in mammals, test for family-specific rates of accumulation, and consider the role of conflict between the sexes or within the genome in the evolution of these systems. We identify 152 species with sex chromosomes that differ from the ancestral state and find evidence for different rates of ancestral to derived transitions among families. Sex chromosome-autosome fusions account for 79% of all variants whereas documented sex chromosome fissions are limited to three species. We propose that meiotic drive and drive suppression provide viable explanations for the evolution of many of these variant systems, particularly those involving autosomal fusions. We highlight taxa particularly worthy of further study and provide experimental predictions for testing the role of conflict and its alternatives in generating observed sex chromosome diversity.