Electroconvulsive therapy (ECT) is a well-established intervention for treatment-resistant major depressive disorder (MDD). Although the neurobiological ramifications of ECT, particularly in relation to the mesolimbic dopaminergic system, have been correlated with the modulation of reward and reinforcement pathways, the capacity of ECT to influence substance-related behaviors remains inadequately elucidated. We report the case of a 42-year-old Iranian woman with a 14-year history of treatment-resistant MDD and no prior history of tobacco or other substance use. Following a second session of inpatient ECT, the patient experienced a sudden and intense craving for cigarettes, leading to the immediate initiation of daily smoking. This pattern of tobacco use persisted for several years, despite multiple motivated attempts at cessation. The patient’s psychiatric management included standard pharmacotherapy and supportive interventions, but ongoing nicotine dependence remained challenging. There was no personal or family history of substance use, and no exposure to smoking in the inpatient setting, aside from a shared room with a smoker in a different ward. To our knowledge, this is the first documented case of cigarette smoking initiation following ECT in a non-smoking patient with MDD. The case underscores the need for heightened clinical vigilance and further investigation into ECT’s effects on addictive vulnerability and reward processing.