We report a method for blocking interactions between 129 Xe and cucurbit[6]uril (CB6) until activation by a specific chemical event.We synthesized a CB6-rotaxane that allowed no 129 Xe interaction with the CB6 macrocycle component until a cleavage event released the CB6, which then produced a 129 Xe@CB6 NMR signal.This contrast-upon-activation 129 Xe NMR platform allows for modular synthesis and can be expanded to applications in detection and disease imaging.