A novel CoAl-hydrotalcite catalyst with different Co2+/Al3+ ratios was facilely synthesized using a modified coprecipitation method. Different techniques such as X-ray diffraction (XRD), Fourier transform-infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), and energy-dispersive X-ray (EDX) were used to characterize the resultant CoAl-hydrotalcite. It was indicated that high crystallinity and a single-phase, layered structure with good composition was successfully fabricated. The resultant CoAl-hydrotalcite catalysts and two comparative hydrotalcites (ZnAl-HT and NiAl-HT) were employed for the selective dehydration of D-fructose into platform chemical 5-hydroxymethylfurfural (HMF), which is a versatile intermediate for the production of biofuels and value-added chemicals. It was shown that the metal variation in Co2+/Al3+ ratios and reaction temperature display clear influence on the catalytic activities. Furthermore, the spent CoAl-hydrotalcite catalysts were easily recycled and show high catalytic stability over three consecutive runs.