Longitudinal data from the Early Grade Reading Study (EGRS I) in South Africa (N = 4538) were used to examine the role of instructional contexts in the relations of literacy skills between children's home language (L1 Setswana) and a second language (L2 English). All children received literacy instruction in Setswana in Grades 1 to 3. However, children in the treatment condition were provided with explicit and systematic Setswana language instruction in phonological awareness and phonics (n = 1964), whereas those in comparison condition received business-as-usual instruction (n = 2574). Children's literacy skills were assessed four times: Time 1 in the beginning of Grade 1, Time 2 at the end of Grade 1, Time 3 at the end of Grade 2, and Time 4 at the end of Grade 4. Literacy data in Setswana were collected in all four time points, whereas data in English were collected in Times 3 and 4. Results from confirmatory factor analysis and structural equation modeling showed that L1 Setswana literacy skill strongly predicted concurrent L2 English reading skill across instructional contexts. However, the longitudinal relation from Grade 2 Setswana literacy skill to Grade 4 English reading skill was found only for those in the treatment condition, but not for those in the comparison condition, after accounting for concurrent relations between Setswana and English. These results suggest that instructional contexts in L1 have implications for the nature relations between L1 and L2 literacy skills.