Weathering often induces bituminous materials adsorbing on the sand grains and leads to poor processability of the oil sands. Chemical and microbial pre-treatment of the prepared weathered ore model and a weathered oil sand ore were carried out to improve the solids surface wettability so as to facilitate the bitumen liberation and recovery. It was found that although all the cetyl trimethylammonium bromide (CTAB), sodium dodecylbenzene sulphonate (SDBS), and microbial culture medium could greatly decrease the surface tension of the solution, the CTAB treatment failed to improve the bitumen liberation, while the SDBS and microbial treatment significantly accelerated the bitumen liberation from the silicon substrates. The wettability analysis showed that the improved bitumen liberation could be attributed to the alteration of the solids surface wettability from hydrophobic to hydrophilic by the SDBS and microbial treatment. Inconsistent with the findings of the bitumen liberation, floatation tests of a weathered ore showed that the CTAB pre-treatment only gave a low bitumen recovery of 33%, while the SDBS and microbial pre-treatment improved the processability of the ore. In particular, the microbial treatment was more effective at removing the adsorbed organics from the solids and improved the surface hydrophilicity, resulting in a much better bitumen recovery of 95%. This work provides a way to improve the processability of the weathered ore by altering the solids surface wettability.