The effects of boron content and preparation methods are studied in this present investigation. Three different methods are employed for the preparation of catalysts. The catalysts are characterized by pore size distribution (PSD), X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Thiophene hydrodesulfurization (HDS), cumene hydrocracking (HC), gas oil HDS and Maya heavy crude oil HDS, and hydrodemetallization (HDM) activities are tested. The results show that the specific surface area and PSD are not changed with B loading. The enrichment of metal distribution on the alumina surface is observed from SEM experiments for the 0.6B-NiMo catalyst. More staging of MoS2 active phases is noticed in the B catalyst than the B-free catalyst. It can be stated that boron forms a monolayer on the alumina surface and reduces the metal-support interaction. It facilitates the formation of more staging of active phases. The thiophene HDS activity slightly increases with boron loading up to 0.6 wt % B, and after that, the activity becomes constant or slightly decreases. The cumene cracking of the NiMo-B catalyst shows the highest activity. The overall activity of boron catalysts was found to be the same or marginally higher than that of the boron-free catalyst. The presence of boron may help to reduce catalyst deactivation during hydrotreating of heavy crude oil.