Spoken language ability is highly heterogeneous in Autism Spectrum Disorder (ASD), which complicates efforts to identify linguistic markers for use in diagnostic classification, clinical characterization, and for research and clinical outcome measurement. Machine learning techniques that harness the power of multivariate statistics and non-linear data analysis hold promise for modeling this heterogeneity, but many models require enormous datasets, which are unavailable for most psychiatric conditions (including ASD). In lieu of such datasets, good models can still be built by leveraging domain knowledge. In this study, we compare two machine learning approaches: the first approach incorporates prior knowledge about language variation across middle childhood, adolescence, and adulthood to classify 6-minute naturalistic conversation samples from 140 age- and IQ-matched participants (81 with ASD), while the other approach treats all ages the same. We found that individual age-informed models were significantly more accurate than a single model tasked with building a common algorithm across age groups. Furthermore, predictive linguistic features differed significantly by age group, confirming the importance of considering age-related changes in language use when classifying ASD. Our results suggest that limitations imposed by heterogeneity inherent to ASD and from developmental change with age can be (at least partially) overcome using domain knowledge, such as understanding spoken language development from childhood through adulthood.