This article introduces a set of teaching strategies to enhance second language learning for students with Down syndrome (DS) enrolled in an English course covering material from the first two years of primary school. A set of instructional support strategies has been defined and integrated into an online learning software, developed ad hoc to teach the basic vocabulary of the English subject syllabus of the two first courses of primary school. A controlled experiment was carried out with 20 students with DS, who were divided into two groups: control and experimental. The control group was given a simplified version of the software, while the experimental group had access to the complete software with personalized instruction. Prior to the experiment, all participants undertook the same level test (pretest) in order to assess their initial knowledge level of English. After finishing the learning stage, a posttest was provided to the students to assess their learning. In both groups, results in the posttest were consistently better than in the pretest, supporting the positive effect of the learning software as an instructional tool. In addition, learning gains were significantly higher in the experimental group, that used the proposed instructional aids.