The Ediacaran to lower Cambrian Lujiaping Formation in South Qinling exhibited extremely high level of Se enrichment, which has provoked extensive concerns since the critical role of Se in paleo-biological evolution and diversification as well as its bidirectional effects on current ecological environment and human health. Because of complex geological setting within South Qinling during the Ediacaran–early Cambrian interval, distribution pattern and mechanism of Se enrichment in Lujiaping Formation have not been fully understood. In this study, therefore, stratigraphic variations of Se concentration and enrichment level together with enrichment mechanism in Lujiaping Formation in the central part of South Qinling were systematically explored. The result showed that, in the whole Lujiaping Formation, Se concentrations varied from 0.19 to 129 μg/g, with an average of 13.28 μg/g. According to the enrichment factor, most of samples can be classified as strong enrichment and anomaly levels (EF = 10–1000) which mainly occurred in organic matter-enriched siliciclatic rocks including mudstone, shale and stone coal seams. Meanwhile, Se enrichment was accompanied with enrichment of Ag, Mo, As, Cd and V in Lujiaping Formation. Various geochemical proxies were collectively employed to identify potential mechanism of Se enrichment. The results indicated that Se was derived from both terrestrial detrital materials and deep hydrothermal fluids. Strong Se anomaly was intimately linked to authigenic enrichment of U and Mo, manifesting advantageous role of euxinic benthic condition to Se accumulation. Besides, weak watermass restriction, intermittent upwelling, high primary productivity and warm and humid climate were also beneficial to ultimate Se enrichment in Lujiaping Formation. This study complemented fundamental data of Se concentration and enrichment degree in strata of the Ediacaran–early Cambrian period in central South Qinling. Meanwhile, preliminary insight of correlation among Se enrichment, sedimentary environment, paleo-climate and biological blooming during the Ediacaran to early Cambrian interval was obtained, which laid the foundation for further researches.