Many food and fuel crops such as sugarcane and switchgrass are allopolyploids, yet our understanding of these organisms is hindered by the large stature and complex genomes that are characteristic of many polyploid plants. Allopolyploid lineages are formed by hybridization between species followed by genome duplication, a process known to cause chromosomal instability, epigenetic reprogramming, gene expression changes, and relaxed selection on some redundant duplicate genes. These myriad changes make polyploids a desirable source of novel genetic variation for plant breeding. However, the precise order in which these genomic events occur, and the timeframes in which they occur, are incompletely understood. The allotetraploid Brachypodium hybridum emerged in nature from the hybridization of the diploid model grass Brachypodium distachyon and another diploid Brachypodium species, B. stacei. To obtain a global overview of the effects of polyploidy on gene expression over evolutionary time, mRNA-seq was performed for both a natural B. hybridum line and a synthetic line made in the laboratory. This analysis is aided by high-quality reference genomes for all three species. Global analyses show that while both hybridization and genome doubling each induce substantial gene expression change alone, the impact is far greater when they occur together. Additionally, gene misregulation is more rampant in the synthetic polyploid than in the natural one. This suggests that polyploidization is characterized by an initial phase of massive change, followed by an acclimation process in which each subgenome returns to a state more like the original parent. Nonetheless, a few dramatic changes of relevance to polyploid biology have persisted in the natural line. The natural and synthetic lines of B. hybridum each represent a snapshot in polyploid evolution, and together they form a timeline of the genomic changes that occur both immediately and long after polyploidization.