The relationship between spirituality at work and occupational and subjective well-being is not a well-recognized area of research. Many studies have indicated the beneficial effects of spiritual activities on employees’ flourishing, but the mechanisms of this influence are still not sufficiently explained. This study aimed to verify the proposed mechanisms that underlie employees’ spirituality, stress at work, and life satisfaction, and the role of gratitude toward the organization in these relationships. It was assumed that employees’ spirituality is indirectly related to stress at work via gratitude toward the organization. In turn, gratitude toward the organization is directly and indirectly related to life satisfaction through stress at work. The study encompassed 754 individuals working in different companies in Poland. In a sample of women, both spirituality dimensions were indirectly related to stress at work and life satisfaction. Among men, only the secular dimension of spirituality, such as attitude toward coworkers, was indirectly related to stress at work and life satisfaction. Gratitude toward the organization was negatively directly related to stress at work and, through this variable, indirectly positively related to life satisfaction. The benefits of employees’ spirituality for their well-being were confirmed, emphasizing a grateful attitude toward the organization as a significant factor in this relationship.