The Qaidam Basin is an internally drained basin located in the northeastern Tibetan Plateau. Presently, over 50% of the basin floor exposes thick (>1 km) sections of Pliocene–Quaternary strata that are deformed by folding and faulting. We investigated this nearly continuous Pliocene–Quaternary sedimentary record for the effects of global climate change and deformation on basin sedimentation. New detailed stratigraphic, magnetostratigraphic, and stable isotope (δ18O, δ13C) data from the Pliocene Shizigou and Pleistocene Qigequan Formations along the southwestern flank of an intrabasin fold within the north-central Qaidam Basin are presented here. Strata reveal climatically controlled, meter-scale parasequences within shallow-lacustrine, marginal-lacustrine, and deltaic lithofacies. Paleocurrents shift from eastward at the base to southwestward for the majority of the section, but they abruptly shift toward the south-southeast in the upper 400 m. Twenty-two magnetozones constrain deposition between 5.2 Ma and ca. 0.8 Ma and reveal that sedimentation rates were fairly constant (474 ± 34 m/m.y.) from 5.2 to 3.0 Ma, after which time rates abruptly decreased to 154 ± 40 mm/yr before increasing again to ∼750 m/m.y. since 1.2 Ma. The δ18O values shift from relatively constant values (avg. −6.8‰, range −9.6‰ to −4.5‰ relative to Vienna Peedee belemnite [VPDB]) to less negative values (avg. -1.2‰, range -1.2‰ to -2.7‰ VPDB) between 3.1 and 2.6 Ma and to extremely variable values (avg. –2.9‰, range −8.3‰ to 4.0‰) after ca. 2.6 Ma. The post–2.6 Ma extreme variability in stable isotopes reflects the same timeframe of enhanced climatic cyclicity associated with Northern Hemisphere glaciation. The δ13C values remain relatively constant (average −4.0‰, range −5.7‰ to -1.0‰) until ca. 0.9 Ma, when the values increase to -0.3‰ (range -1.0‰ to 1.5‰) VPDB. The appearance of growth strata at 3.0 Ma, shallow-water, evaporite deposition after 2.6 Ma, and the observation of paleoyardangs (buried, wind-sculpted landforms) within lake-marginal strata at 2.4 Ma imply that emergence of the adjacent anticline was followed by the shallowing and partitioning of the lake basin and subaerial exposure and erosion of marginal lake sediments. These data reflect a significant change to a more arid climate in the Qaidam Basin between ca. 3.1 Ma and 2.6 Ma, overlapping with the onset of significant Northern Hemisphere glaciations and basin-floor deformation. Lake-level cycles were on ∼230,000 yr frequency from 2.6 Ma to 1.2 Ma, before increasing to ∼12,000 yr frequency, suggesting increased aridity and broad, subaerial exposure of lake sediments after the Pliocene-Quaternary transition. Deformation of intrabasin sediments by at least 3.0 Ma caused uplift of the basin floor, which provided an environment rich in friable material for wind deflation of the Qaidam Basin, a likely source for sediments on the Chinese Loess Plateau and nutrients for the Pacific Ocean carried by westerly winds. By 2.6 Ma, deformation of the Qaidam Basin created closed depressions that facilitated evaporite sedimentation that continues today. Coeval intrabasin deformation, combined with increasing aridity after 3.1 Ma, thus controlled both deposition and erosion within the region.