A rotaxane actuator enables force-controlled release of small molecules. This system uses a rotaxane, an interlocked molecule with a macrocycle on a stoppered axle, to trigger the release of cargo molecules attached to the axle. The release occurs through mechanochemical scission of covalent bonds when the macrocycle is mechanically activated. In solution, ultrasonication and in bulk, compression, were used to activate the rotaxane. Up to five cargo molecules per rotaxane were released, with efficiencies of 71% in solution and 30% in bulk. The system was tested with three representative functional molecules: a drug, a fluorescent tag, and an organocatalyst. The rotaxane architecture allows for the sequential release of multiple cargo molecules due to its unique pushing mechanism. The design involves a pillar[5]arene macrocycle threaded onto a C12 alkyl chain, with polymer chains attached to the axle and macrocycle for mechanical activation. The cargo molecules are loaded onto the axle via a Diels–Alder reaction, and their release is triggered when the macrocycle encounters steric obstacles. The study demonstrates the versatility and efficiency of the rotaxane actuator for force-controlled release applications, with potential for a wide range of cargo molecules. The system shows high release efficiency and the ability to release different cargo units in a defined sequence. The rotaxane actuator is a promising platform for various force-controlled release applications in medical and materials contexts.A rotaxane actuator enables force-controlled release of small molecules. This system uses a rotaxane, an interlocked molecule with a macrocycle on a stoppered axle, to trigger the release of cargo molecules attached to the axle. The release occurs through mechanochemical scission of covalent bonds when the macrocycle is mechanically activated. In solution, ultrasonication and in bulk, compression, were used to activate the rotaxane. Up to five cargo molecules per rotaxane were released, with efficiencies of 71% in solution and 30% in bulk. The system was tested with three representative functional molecules: a drug, a fluorescent tag, and an organocatalyst. The rotaxane architecture allows for the sequential release of multiple cargo molecules due to its unique pushing mechanism. The design involves a pillar[5]arene macrocycle threaded onto a C12 alkyl chain, with polymer chains attached to the axle and macrocycle for mechanical activation. The cargo molecules are loaded onto the axle via a Diels–Alder reaction, and their release is triggered when the macrocycle encounters steric obstacles. The study demonstrates the versatility and efficiency of the rotaxane actuator for force-controlled release applications, with potential for a wide range of cargo molecules. The system shows high release efficiency and the ability to release different cargo units in a defined sequence. The rotaxane actuator is a promising platform for various force-controlled release applications in medical and materials contexts.