Speech intelligibility measures how much a speaker can be understood by a listener. Traditional measures of intelligibility, such as word accuracy, are not sufficient to reveal the reasons of intelligibility degradation. This dissertation investigates the underlying sources of intelligibility degradations from both perspectives of the speaker and the listener. Segmental phoneme errors and suprasegmental lexical boundary errors are developed to reveal the perceptual strategies of the listener. A comprehensive set of automated acoustic measures are developed to quantify variations in the acoustic signal from three perceptual aspects, including articulation, prosody, and vocal quality. The developed measures have been validated on a dysarthric speech dataset with various severity degrees. Multiple regression analysis is employed to show the developed measures could predict perceptual ratings reliably. The relationship between the acoustic measures and the listening errors is investigated to show the interaction between speech production and perception. The hypothesize is that the segmental phoneme errors are mainly caused by the imprecise articulation, while the sprasegmental lexical boundary errors are due to the unreliable phonemic information as well as the abnormal rhythm and prosody patterns. To test the hypothesis, within-speaker variations are simulated in different speaking modes. Significant changes have been detected in both the acoustic signals and the listening errors. Results of the regression analysis support the hypothesis by showing that changes in the articulation-related acoustic features are important in predicting changes in listening phoneme errors, while changes in both of the articulation- and prosody-related features are important in predicting changes in lexical boundary errors. Moreover, significant correlation has been achieved in the cross-validation experiment, which indicates that it is possible to predict intelligibility variations from acoustic signal.