Sleep plays an active role in memory consolidation. Because children with Down syndrome (DS) and Williams syndrome (WS) experience significant problems with sleep and also with learning, we predicted that sleep-dependent memory consolidation would be impaired in these children when compared to typically developing (TD) children. This is the first study to provide a cross-syndrome comparison of sleep-dependent learning in school-aged children. Children with DS (n = 20) and WS (n = 22) and TD children (n = 33) were trained on the novel Animal Names task where they were taught pseudo-words as the personal names of ten farm and domestic animals, e.g. Basco the cat, with the aid of animal picture flashcards. They were retested following counterbalanced retention intervals of wake and sleep. Overall, TD children remembered significantly more words than both the DS and WS groups. In addition, their performance improved following night-time sleep, whereas performance over the wake retention interval remained stable, indicating an active role of sleep for memory consolidation. Task performance of children with DS did not significantly change following wake or sleep periods. However, children with DS who were initially trained in the morning continued to improve on the task at the following retests, so that performance on the final test was greater for children who had initially trained in the morning than those who trained in the evening. Children with WS improved on the task between training and the first retest, regardless of whether sleep or wake occurred during the retention interval. This suggests time-dependent rather than sleep-dependent learning in children with WS, or tiredness at the end of the first session and better performance once refreshed at the start of the second session, irrespective of the time of day. Contrary to expectations, sleep-dependent learning was not related to baseline level of performance. The findings have significant implications for educational strategies, and suggest that children with DS should be taught more important or difficult information in the morning when they are better able to learn, whilst children with WS should be allowed a time delay between learning phases to allow for time-dependent memory consolidation, and frequent breaks from learning so that they are refreshed and able to perform at their best.