Background: COVID-19 has resulted in some educators and allied health practitioners transitioning to online delivery of literacy instruction. As far as we are aware, no studies have investigated online delivery of comprehensive literacy instruction for children with Down syndrome. Aims: In this pilot study, we explore the efficacy of online delivery of ABRACADABRA (a free literacy web application) for children with Down syndrome, alongside supplementary parent-led shared book reading, during the COVID-19 pandemic. Sample: Six children with Down syndrome, aged 8-12 years, participated in this within-participants design study. Methods: Participants acted as their own controls with outcome variables measured at three timepoints: baseline, pre-instruction and post-instruction. Children participated in 16-18 hrs of one-to-one literacy instruction online over a 6-week instruction phase, along with twice weekly parent-led shared book reading activities. Results: Outcomes from standardized assessments revealed statistically significant improvements in word- and passage-level reading accuracy skills over the instruction phase (pre-instruction to post-instruction) compared with the no-instruction control phase (baseline to pre-instruction). Improvements in reading comprehension skills were inconsistent across assessment measures and statistical analyses. Conclusion: Children with Down syndrome can benefit from comprehensive literacy instruction delivered via telepractice. Our study provides critical initial evidence of successful service delivery during a global pandemic and beyond.