Somatic cell reprogramming into induced pluripotent stem cells (iPSCs) induces changes in genome architecture reflective of the embryonic stem cell (ESC) state. However, only a small minority of cells typically transition to pluripotency, which has limited our understanding of the process. Here, we characterize the DNA regulatory landscape during reprogramming by time-course profiling of isolated sub-populations of intermediates poised to become iPSCs. Widespread reconfiguration of chromatin states and transcription factor (TF) occupancy occurs early during reprogramming, and cells that fail to reprogram partially retain their original chromatin states. A second wave of reconfiguration occurs just prior to pluripotency acquisition, where a majority of early changes revert to the somatic cell state and many of the changes that define the pluripotent state become established. Our comprehensive characterization of reprogramming-associated molecular changes broadens our understanding of this process and sheds light on how TFs access and change the chromatin during cell-fate transitions. Display omitted •Regulatory element accessibility during reprogramming reveals distinct dynamic phases•Oct4/Sox2 recruit somatic transcription factors to transiently accessible sites•Oct4/Sox2 preferentially bind to closed chromatin in MEFs•Profiling of cells that fail to reprogram reveals they maintain a MEF chromatin state Knaupp and Buckberry et al. show that during reprogramming cells undergo major chromatin remodeling in three phases. Further, they find that Oct4 and Sox2 extensively target sites where the DNA is only accessible during the intermediate stages of reprogramming, which coincides with somatic transcription factor displacement and recruitment to those sites.