Abstract: Software testing is essential for the reliable and robust development of complex software systems. A key step in software testing is fault localization, which uses test data to pinpoint failure-inducing combinations for further diagnosis. Existing fault localization methods have two key limitations: they (i) do not incorporate domain and/or structural knowledge from test engineers, and (ii) do not provide a probabilistic assessment of risk for potential root causes. Such methods can thus fail to confidently whittle down the combinatorial number of potential root causes in complex systems, resulting in prohibitively high testing costs. To address this, we outline a holistic machine-learning-guided test case design and fault localization (MaLT) framework, which leverages recent probabilistic machine learning methods to accelerate the testing of complex software systems. MaLT consists of three steps: (i) the construction of a suite of test cases using a covering array for initial testing, (ii) the investigation of posterior root cause probabilities via a Bayesian fault localization procedure, then (iii) the use of such Bayesian analysis to guide selection of subsequent test cases via active learning. The proposed MaLT framework can thus facilitate efficient identification and subsequent diagnosis of software faults with limited test runs.