Many rivers are tightly coupled and intersected with aeolian sand dunes, whose geomorphological evolution involves not only fluvial processes but also aeolian processes that pose a new challenge to fluvial geomorphological studies. However, due to few field studies, our overall understanding of the desert channel geomorphic process is limited. In this paper, we present an outstanding example of desert river channel evolution regulated by aeolian–fluvial interactions in the Ulan Buh Desert of the Yellow River, based on a long time series data set (1966–2019) of channel cross-sections. The results indicate that the lateral addition of aeolian sand, the water–sediment relationship and human interference have a significant role at different periods of channel evolution. Before 1986, higher discharge, lower sediment content and greater intensity of aeolian activity caused aeolian–fluvial interactions and a relative scouring and silting balance in the channel, with little human activity. From 1986 to 2000, an increase in large reservoir operation, vegetation coverage and floodplain farming, coupled with water–sediment relationship variation, caused rapid deposition and shrinkage of the river channel. From 2000 to 2014, the channel kept a slight scouring state. With Haibowan reservoir operation beginning in 2014, the talweg experienced rapid scouring and undercut rebound. However, an expanding and stable floodplain accelerated sedimentation on the floodplain and weakened river lateral erosion, indicating that the channel has shown a shrinkage trend. Meanwhile, wavelet analysis results indicate that human interferences and aeolian activities have no significant role in the periodical characteristics of the channel’s longitudinal erosion and deposition. Therefore, on the whole, increasing human interferences and decreasing wind dynamics have driven this desert wandering channel to be stable, and to gradually form a new balance between erosion and sedimentation.