We tested the theoretically driven hypotheses that children's orthographic and semantic learning are associated with their word reading and reading comprehension skills, even when orthographic and semantic knowledge are taken into account. A sample of 139 English-speaking Grade 3 children completed a learning task in which they read stories about new inventions. Then they were tested on their learning of the spelling and meaning of the inventions (i.e., orthographic and semantic learning, respectively). Word reading and reading comprehension were assessed with standardised tasks, and orthographic and semantic knowledge were assessed with choice tasks targeting the spelling and meaning of existing words. The results of our structural equation modeling indicated that orthographic learning predicted word reading directly and reading comprehension indirectly via word reading. We also found that semantic learning predicted reading comprehension directly. These findings support integration of the self-teaching hypothesis and the lexical quality hypothesis.