Far from being mere inanimate natural occurrences, river flows around the world are sites where natural phenomena intersect with cultural traditions. From this intersection and interaction a range of rich cultural values, beliefs, meanings and social significances emerge and persist. Drawing on this understanding of rivers as coupled natural and human systems, this dissertation is a broad ethnographic investigation and interpretation of the cultural significance of River Abay (hereafter Abay) in Ethiopia. Specifically, the research explored spiritual beliefs and practices, and symbolic meanings linked with Abay, as well as the distinct ecological elements of those beliefs and practices. Ethnographic, and to some extent historical information informing the study, was collected through a combination of in-depth interviews and participant observation among communities residing along the river in Wetet Abay town and its rural vicinities. Some popular Amharic proverbs, poems and song verses about Abay were also included and interpreted to provide the research a folkloric context, in order to better grasp the symbolic meanings associated with the river. Along with some empirical studies relevant to the topic, the firsthand data were analyzed through thematic and content analysis methods. The findings reveal that, in the eyes of local people, Abay is concurrently imbued with holy powers and untamed supernatural beings. This notion, in particular, has made Abay a spiritually significant site for invoking the mediation and protection of supernatural forces through rituals and sacrifices conducted along the river. Symbolically, Abay is perceived via a humanized lens, with its natural features profoundly embodied as metaphorical and figurative elements in the language used to express diverse phenomena and aspects of people’s lives. The cultural values, especially the spiritual beliefs and practices associated with Abay, possess important ecological elements, contributing to conservation along the river, particularly in the protection of trees. The [viii] findings imply that, there is an overall decline in the frequency and regularity of magico religious rituals and sacrifices along the river. In addition, at the state level, the river’s cultural features are overlooked in favor of focusing on its economic aspects. However, despite the decline of rituals and the policy neglect, the imagery of Abay as religiously holy, as well as home of powerful invisible beings affecting the welfare of humans remains enduring. Abay also persists as a common and distinctive natural and cultural icon for the Ethiopian people, where its real and symbolic presence has profound and lasting imprint in the traditions of local communities and the imaginations of individuals.