Knowing how switchgrass (Panicum virgatum L.) responds and adapts to phosphorus (P)-limitation will aid efforts to optimize P-efficiency in this species for sustainable biomass production. This integrative study investigated the impacts of mild, moderate, and severe P-stress on genome transcription and whole-plant metabolism, physiology and development in an unprecedented way for this species. P-limitation reduced overall plant growth, increased root/shoot ratio, increased root branching at moderate P-stress, and decreased root diameter with increased density and length of root hairs at severe P-stress. RNA-seq analysis revealed thousands of genes that were differentially expressed under moderate and severe P-stress in roots and/or shoots compared to P-replete plants, with many stress-induced genes involved in transcriptional and other forms of regulation, primary and secondary metabolism, transport, and other processes involved in P-acquisition and homeostasis. Amongst the latter were multiple miRNA399 genes and putative targets of these. Metabolite profiling showed that levels of most sugars and sugar alcohols decreased with increasing P stress, while organic and amino acids increased under mild and moderate P-stress in shoots and roots, although this trend reversed under severe P-stress, especially in shoots.