Many smart MRI probes provide response to a biomarker based on modulation of their rotational correlation time. The magnitude of such MRI signal changes is highly dependent on the magnetic field and the response decreases dramatically at high fields (> 2 T). To overcome the loss of efficiency of responsive probes at high field, with FFC‐MRI we exploit field‐dependent information rather than the absolute difference in the relaxation rate measured in the absence and in the presence of the biomarker at a given imaging field. We report here the application of fast field‐cycling techniques combined with the use of a molecular probe for the detection of Zn2+ to achieve 166% MRI signal enhancement at 3 T, while the same agent provides no detectable response using conventional MRI. This approach can be generalized to any biomarker provided the detection is based on variation of the rotational motion of the probe.