Scientific development has been a significant instrument and factor in the advancement of Islamic civilization. However, from the Middle Ages onward, it encountered obstacles and challenges which, despite the presence of valuable achievements and the nurturing of numerous scholars, led to its decline. Consequently, it failed to provide the necessary grounds for the scientific development of Islamic societies in accordance with the exigencies of the time. Therefore, identifying the causes of this scientific decline is essential for removing the barriers to progress and achieving prosperity and development. This issue has attracted the attention of scholars in the fields of science and civilization, each of whom has examined it from a particular perspective and enumerated various causes for it. Among these, familiarity with the thoughts of Imam Khomeini (RA) can contribute to a better understanding of the fundamental causes of the scientific decline and how to confront them. Thus, employing a descriptive-analytical method, this paper investigates the essential causes of the scientific decline in the Islamic World from his perspective. The findings indicate that Imam Khomeini (RA) considered the role of internal causes—such as a lack of self-belief and the avoidance of reason and intellect—as more significant than external causes in the scientific decline. He enumerated colonialism in its various dimensions (e.g., intellectual, infiltration) among the external causes. Accordingly, he proposed solutions such as scientific self-sufficiency, self-confidence, the alignment of science with Islamic values, and cooperation among scientific centers to overcome this challenge.