The current study examined the effectiveness of a reading curriculum of explicit instruction on the letter-sound knowledge of a sample of elementary-aged students with Down syndrome. The procedures were adapted from prior research (King et al., 2020; Lemons et al., 2018; Lemons et al., 2015). Three participants between 9 and 11 years old participated in the study. Participants were provided with five lessons or 5 tiers of data points on letter-sound knowledge, wherein they practiced identifying initial letter-sounds from highly imageable and decodable words. Unique to this study was the addition of explicit instruction procedures in spelling and measurement of improved spelling skills for both taught and untaught words. We used a multiple probe design across intervention lessons. Letter-sound accuracy increased for all three participants. Results for the spelling outcomes were mixed, with most students making minimal progress. Improvements in letter-sound knowledge did not naturally transfer to the spelling outcome, supporting the idea that explicit instruction may be necessary to support the transfer of skills for children with Down syndrome.