late 14c., mortifien, "to kill, destroy the life of," from Old French mortefiier "destroy, overwhelm, punish," from Late Latin mortificare "cause death, kill, put to death," literally "make dead," from mortificus "producing death," from Latin mors (genitive mortis) "death" (from PIE root *mer- "to rub away, harm," also "to die" and forming words referring to death and to beings subject to death) + combining form of facere "to make, to do" (from PIE root *dhe- "to set, put").
Religious sense of "subdue the flesh by abstinence and discipline" is attested from early 15c. Sense of "humiliate, chagrin, vex" is recorded by 1690s (compare mortification). Related: Mortified; mortifying.