English serves as today’s lingua franca, a role not eased by the inconsistency of its orthography. Indeed, monolingual readers of more consistent orthographies such as Italian or German learn to read more quickly than monolingual English readers. Here, we assessed whether long-lasting bilingualism would mitigate orthography-specific differences in reading speed and whether the order in which orthographies with a different regularity are learned matters. We studied high-proficiency Italian-English and English-Italian bilinguals, with at least 20 years of intensive daily exposure to the second language and its orthography and we simulated sequential learning of the two orthographies with the CDP++ connectionist model of reading. We found that group differences in reading speed were comparatively bigger with Italian stimuli than with English stimuli. Furthermore, only Italian bilinguals took advantage of a blocked presentation of Italian stimuli compared to when stimuli from both languages were presented in mixed order, suggesting a greater ability to keep language-specific orthographic representations segregated. These findings demonstrate orthographic constraints on bilingual reading, whereby the level of consistency of the first learned orthography affects later learning and performance on a second orthography. The computer simulations were consistent with these conclusions.