The timing of the origin of arthropods in relation to the Cambrian explosion is still controversial, as are the timing of other arthropod macroevolutionary events such as the colonization of land and the evolution of flight. Here we assess the power of a phylogenomic approach to shed light on these major events in the evolutionary history of life on earth. Analyzing a large phylogenomic dataset (122 taxa, 62 genes) with a Bayesian-relaxed molecular clock, we simultaneously reconstructed the phylogenetic relationships and the absolute times of divergences among the arthropods. Simulations were used to test whether our analysis could distinguish between alternative Cambrian explosion scenarios with increasing levels of autocorrelated rate variation. Our analyses support previous phylogenomic hypotheses and simulations indicate a Precambrian origin of the arthropods. Our results provide insights into the 3 independent colonizations of land by arthropods and suggest that evolution of insect wings happened much earlier than the fossil record indicates, with flight evolving during a period of increasing oxygen levels and impressively large forests. These and other findings provide a foundation for macroevolutionary and comparative genomic study of Arthropoda.