This study used the nature of indigenous knowledge (NOIK) framework to explore indigenous knowledge systems (IKS) practices that were integrated when practical work in natural sciences was facilitated. In this interpretive explorative case study, data were collected by semistructured interviews, lesson observations and a focus group interview conducted with three purposively selected natural sciences teachers and two natural sciences district officials in the province of KwaZulu-Natal in South Africa. Thematic analysis techniques were used to analyze the data that were collected. Three findings on ways to integrate IKS in science practical work are the following. First, IKS was integrated in practical work through teaching of applied science and including the learners’ lived experiences of local technologies to solve problems. Second, practical work that integrated IKS was conducted as empirical observations of natural phenomena, which included genetic variation of plants and animals, including human beings, animal behavior, using moon cycles and the movement of the sun to guide day-to-day, cultural and agricultural activities. Third, some of the IKS included myths and superstitions that distorted the public understanding of science but were nevertheless used to persuade people to uphold certain cultural practices. The study recommends comparing NOIK and the nature of science when integrating IKS in the classroom to enable learners to distinguish myths from scientific facts.