The uplift history of the Colorado Plateau has been debated for over a century with still no unified hypotheses for the cause, timing, and rate of uplift. 40 Ar/ 39 Ar and K/Ar dating of recurrent basaltic volcanism over the past ~6 Ma within the Virgin River drainage system, southwest Utah, northwest Arizona, and southern Nevada, provides a way to reconstruct paleoprofiles and quantify differential river incision across the boundary faults of the Colorado Plateau-Basin and Range boundary. We compare differential incision data with patterns of channel steepness, bedrock erodibility, basaltic migration, and mantle velocity structure to understand the birth and evolution of the Virgin River system. New detrital sanidine ages constrain the arrival of the Virgin River across the Virgin Mountains to less than 5.9 Ma. Virgin River incision rates and amounts show an eastward stair-step increase in bedrock incision across multiple N-S-trending normal faults. Using block incision values away from fault-related flexures, average bedrock incision rates are near zero since 4.6 Ma in the Lower Colorado River corridor, 23 m/Ma from 6.8 to 3.6 Ma in the Lake Mead block, 85 m/Ma from 3 to 0.4 Ma in the combined St. George and Hurricane blocks, and 338 m/Ma from 1 to 0.1 Ma in the Zion block. Steady incision within each block is documented by incision constraints that span these age ranges. We test two end-member hypotheses to explain the observed differential incision magnitudes and rates along the Virgin River system over the past ~5 Ma: (1) as a measure of mantle-driven differential uplift of the Colorado Plateau relative to sea level; or (2) due to river integration across previously uplifted topography and differential rock types with down-dropping of Transition Zone blocks but no post-5 Ma uplift. We favor headwater uplift of the Colorado Plateau because basalt-preserved paleoprofiles indicate that eastern fault blocks have been the "active" blocks that moved upwards relative to western blocks with little base-level change of the lower Colorado River corridor in the past 4.6 Ma. Block-to-block differential incision adds cumulatively such that the Zion block (Colorado Plateau edge) has been deeply incised 880-1200 m (~338 m/Ma) over the 2.6-3.6 Ma period of Hurricane fault neotectonic movement, which has a slip magnitude of 1100 m. Mantle-driven uplift is implicated by a strong correlation throughout the Virgin River drainage between high normalized channel steepness (k sn) and low underlying mantle velocity, whereas there is a weaker correlation between high k sn and resistant lithologies. Basaltic volcanism has migrated northeastward at a rate of ~18 km/Ma parallel to the Virgin River between ca. 13 and 0.5 Ma, also suggesting a mantle-driven mechanism for the combined epeirogenic uplift of the western Colorado Plateau, recurrent slip on its bounding faults, and headward propagation and differential incision of the Virgin River. Thus, we interpret the Virgin River to be a <5 Ma disequilibrium river system responding to ong...