Patchouli alcohol (PA), a tricyclic sesquiterpene, is the major chemical component of patchouli oil. This study investigated the antidepressant-like effect and mechanism of PA in chronic unpredictable mild stress (CUMS). Our results showed that PA markedly attenuated CUMS-induced depressant-like behaviors, including an effective increase of sucrose preference and spontaneous exploratory capacity, as well as reduction of immobility time. In addition, PA markedly attenuated CUMS-induced mTOR, p70S6K, and 4E-BP-1 phosphorylation reduction in the hippocampus. Furthermore, PA reversed CUMS-induced increases in LC3-II and p62 levels and CUMS-induced decrease in PSD-95 and SYN-I levels. These results indicated that the antidepressant-like effect of PA was correlated with the activation of the mTOR signaling pathway. Moreover, behavioral experimental results showed that the antidepressant-like effect of PA was blocked by rapamycin (autophagy inducer and mTOR inhibitor) and chloroquine (autophagic flux inhibitor). These results suggest that PA exerted antidepressant-like effect in CUMS rats through inhibiting autophagy, repairing synapse, and restoring autophagic flux in the hippocampus by activating the mTOR signaling pathway. The results render PA a promising antidepressant agent worthy of further development into a pharmaceutical drug for the treatment of depression.