Controlling the rate at which polymers break down is essential for developing sustainable materials. Conventional approaches—which rely on introducing labile and cleavable bonds—often face an inherent trade-off between stability and ease of deconstruction. Inspired by self-deconstruction mechanisms in biomacromolecules, we leverage conformational preorganization of neighbouring groups to modulate and expedite polymer self-deconstruction. Here we show that precise spatial alignment of nucleophilic groups relative to labile bonds regulates the cleavage kinetics by shifting the conformational ensemble towards reactive geometries. This strategy enables programmable deconstruction of both linear polymers and bulk thermosetting networks under ambient conditions, with rates tunable across several orders of magnitude—without altering the chemical identity of the cleavable bond or compromising the polymers’ physical properties. Furthermore, even distal intramolecular functionalities can be harnessed to dynamically control bond cleavability through metal-induced polymer folding, enabling reversible activation and deactivation of self-deconstruction. This work establishes conformational control as a powerful strategy for fine-tuning polymer deconstruction. Cleavable bonds are a central strategy for polymer deconstruction, but controlling the rate of breakdown remains difficult because it is dictated by intrinsic bond cleavage kinetics. Now it has been shown that bio-inspired conformationally preorganized neighbouring groups enable programmable polymer deconstruction without changing the cleavable bond itself or compromising material properties.