With the development of autonomous driving technology, it is foreseeable that connected and automated vehicles (CAVs) will be fully popularized in people’s lives. During this process, transportation systems are expected to evolve into the era of mixed autonomy, where CAVs and human-driven vehicles (HDVs) coexist in road networks and share available road resources. To materialize the much-anticipated potential of CAVs, a thorough understanding of CAVs’ effects on transportation systems is indispensable. On the one hand, attributing to advanced sensing, communication, and computation capabilities, CAVs provide opportunities to enhance mixed traffic safety, improve energy savings and suppress shockwave spread. On the other hand, due to advantages in large-scale information and cloud-computing resources, CAVs have the ability to occupy more road resources compared with HDVs, resulting in a reduction in the travel efficiency of HDVs, and even of the entire transportation systems. In this article, by clarifying the key differences between HDVs and CAVs, we comprehensively review the potential impacts of CAVs when they are appearing on road networks coexisting with HDVs. It can be regarded as the first-of-its-kind paper that systematically overviews the impacts of CAVs in the era of mixed autonomy on both positive and negative emotions. Specifically, the main focuses of this article are: 1) what are the key differences between CAVs and HDVs? 2) what are the positive impacts of CAVs’ appearance on mixed traffic systems? 3) will the introduction of CAVs cause some negative effects simultaneously? and 4) what kinds of strategies should be employed to relieve these negative effects? Hopefully, this article can not only call for an objective attitude toward the introduction of CAVs, but also provide foresighted advice to address possible challenges during the popularization of CAVs, so as to create a cooperative, safe, and efficient mixed traffic ecosystem.