The catalytic conversion of palmitic acid was studied over Co/SiO2, H‐ZSM‐22 (HZ‐22), Co/H‐ZSM‐22 (Co/HZ‐22), mesoporous H‐ZSM‐22 (HZP‐22), and Co/H‐ZSM‐22 (Co/HZP‐22) catalysts. For the bifunctional catalysts, on the one hand, the porosity of zeolitic supports provided uniform accommodation for Co particles to realize the good distribution and downsizing of metal particles; on the other hand, the impregnation of Co into zeolitic supports improved the acidity of bifunctional catalysts that presented more weak/strong acid sites and stronger acid strength. Compared to sole metal centers over Co/SiO2 (no isomerization), the hydrodeoxygenation and hydroisomerization of palmitic acid were achieved simultaneously over bifunctional Co/HZ‐22 and Co/HZP‐22 catalysts (4 wt % Co loading) in one step. Mesoporous Co/HZP‐22 possessed an excellent catalytic performance during the upgrading of palmitic acid to yield the highest amount of iso‐alkanes. Importantly, the metal/zeolite bifunctional catalysts tailored the deoxygenation route significantly from hydrodecarbonylation (major) over sole metal catalysts or zeolites (only metal centers and only acid sites) to the hydrodeoxygenation route (major) over Co/zeolite bifunctional catalysts (both metal centers and acid sites).