Offering reward during encoding typically leads to better memory [Adcock, R. A., Thangavel, A., Whitfield-Gabrieli, S.,Knutson, B., & Gabrieli, J. D. E. Reward-motivated learning: Mesolimbic activation precedes memory formation. Neuron, 50, 507–517, 2006]. Whether such memory benefit persists when tested in a different task context remains, however, largely understudied [Wimmer, G. E., & Buechel, C. Reactivation of reward-related patterns from single past episodes supports memory-based decision making. Journal of Neuroscience, 36, 2868–2880, 2016]. Here, we ask whether reward at encoding leads to a generalized advantage across learning episodes, a question of high importance for any everyday life applications, from education to patient rehabilitation. Although we confirmed that offering monetary reward increased responses in the ventral striatum and pleasantness judgments for pictures used as stimuli, this immediate beneficial effect of reward did not carry over to a subsequent and different picture–location association memory task during which no reward was delivered. If anything, a trend for impaired memory accuracy was observed for the initially high-rewarded pictures as compared to low-rewarded ones. In line with this trend in behavioral performance, fMRI activity in reward (i.e., ventral striatum) and in memory (i.e., hippocampus) circuits was reduced during the encoding of new associations using previously highly rewarded pictures (compared to low-reward pictures). These neural effects extended to new pictures from same, previously highly rewarded semantic category. Twenty-four hours later, delayed recall of associations involving originally highly rewarded items was accompanied by decreased functional connectivity between the hippocampus and two brain regions implicated in value-based learning, the ventral striatum and the ventromedial PFC. We conclude that acquired reward value elicits a downward value-adjustment signal in the human reward circuit when reactivated in a novel nonrewarded context, with a parallel disengagement of memory–reward (hippocampal–striatal) networks, likely to undermine new associative learning. Although reward is known to promote learning, here we show how it may subsequently hinder hippocampal and striatal responses during new associative memory formation.