The Amundsen Sea Embayment of West Antarctica is today the site of pronounced glacial retreat and mass loss. Very little information is available on how the area looked like before the onset of large-scale continental glaciation, and on which morphologic boundary conditions finally led to the onset of glaciation. Here we report data from the first drilling campaign on the Amundsen Sea continental shelf, using the MeBo drilling system. We obtained coarse-grained sediments deposited during the Eocene, shortly before major ice sheet buildup. Our findings reveal the Eocene as a transition period from >40 million years of relative tectonic quiescence toward reactivation of the West Antarctic Rift System, coinciding with incipient volcanism, rise of the Transantarctic Mountains, and renewed sedimentation under temperate climate conditions. The recovered sediments were deposited in a coastal-estuarine swamp environment at the outlet of a >1500-km-long transcontinental river system, draining from the rising Transantarctic Mountains into the Amundsen Sea. Much of West Antarctica hence lied above sea level, but low topographic relief combined with low elevation inhibited widespread ice sheet formation.