Hydrophobic melamine sponges were prepared via a facile one-step reaction of three isocyanates (i.e., cyclohexyl isocyanate, octadecyl isocyanate, and butyl isocyanate) with hydroxymethyl groups located on the melamine sponge. The modified sponges were characterized by infrared spectroscopy, scanning electron microscope, X-ray photoelectron spectroscopy, and contact angle tester. The results showed that the water contact angle of the modified sponges reached around 140°, and the sponges had a three-dimensional network with high porosity, which can be used as efficient adsorbents to adsorb a variety of oils or organic solvents with different viscosities and densities. The experiments found that the modified sponges had good oil absorption performance, with 62–143 times their weight, for different oil and organic solvents. In addition, after being soaked in strong acid, strong alkali, and 3.5% sodium chloride aqueous solutions for 72 h, the modified sponges’ absorption capacity remained high.