Angiosperms are the most successful plants and support human livelihood and ecosystems. Angiosperm phylogeny is the foundation of studies of gene function and phenotypic evolution, divergence time estimation and biogeography. The relationship of the five divergent groups of the Mesangiospermae (~99.95% of extant angiosperms) remains uncertain, with multiple hypotheses reported in the literature. Here transcriptome data sets are obtained from 26 species lacking sequenced genomes, representing each of the five groups: eudicots, monocots, magnoliids, Chloranthaceae and Ceratophyllaceae. Phylogenetic analyses using 59 carefully selected low-copy nuclear genes resulted in highly supported relationships: sisterhood of eudicots and a clade containing Chloranthaceae and Ceratophyllaceae, with magnoliids being the next sister group, followed by monocots. Our topology allows a re-examination of the evolutionary patterns of 110 morphological characters. The molecular clock estimates of Mesangiospermae diversification during the late to middle Jurassic correspond well to the origins of some insects, which may have been a factor facilitating early angiosperm radiation.