Machine learning with deep neural networks (DNNs) has become one of the foundation techniques in many safety-critical systems, such as autonomous vehicles and medical diagnosis systems. DNN-based systems, however, are known to be vulnerable to adversarial examples (AEs) that are maliciously perturbed variants of legitimate inputs. While there has been a vast body of research to defend against AE attacks in the literature, the performances of existing defense techniques are still far from satisfactory, especially for adaptive attacks, wherein attackers are knowledgeable about the defense mechanisms and craft AEs accordingly. In this work, we propose a multilayer defense-in-depth framework for AE detection, namely MixDefense. For the first layer, we focus on those AEs with large perturbations. We propose to leverage the `noise features extracted from the inputs to discover the statistical difference between natural images and tampered ones for AE detection. For AEs with small perturbations, the inference result of such inputs would largely deviate from their semantic information. Consequently, we propose a novel learning-based solution to model such contradictions for AE detection. Both layers are resilient to adaptive attacks because there do not exist gradient propagation paths for AE generation. Experimental results with various AE attack methods on image classification datasets show that the proposed MixDefense solution outperforms the existing AE detection techniques by a considerable margin.