In water, a remarkable motion can be observed with a [2]rotaxane, wherein the rotor translocates by reeling its axle in the cavity of an altro-α-CD stopper. Similarly, in aqueous solution, an alkyl altro-α-CD dimer reels its alkyl chain in the altro-α-CD cavity to form a pseudo[1]rotaxane dimer. This reeling motion is in fact induced by the tumbling of the altropyranose unit of an altro-α-CD, a process shown to be solvent-dependent. Tumbling, however, does not occur in low-polarity solvents such as methanol and DMSO. In the present contribution, the mechanism that underlies solvent-controlled tumbling has been studied at the atomic level by means of molecular dynamics simulations combined with microsecond-timescale free-energy calculations. The free-energy profile delineating the tumbling in water of the altropyranose unit of an alkyl altro-α-CD indicates that a 19.8 kcal mol⁻¹ barrier must be overcome to yield the self-inclusion complex, which is the most stable state available to the supramolecular assembly. In DMSO, the free-energy barrier is about 21.0 kcal mol⁻¹ higher, and the self-included alkyl altro-α-CD corresponds to a metastable state. These results provide new thermodynamic and kinetic insights into solvent-controlled tumbling, and reveal the essence of different experimental observations. Further investigation shows that aside from the polarity of the solvent, tumbling of the altro-α-CD derivative stems from the hydrophobicity of the side chain and the propensity of the former to include the latter, which opens perspectives for the design of new, related supramolecular assemblies.