Spacecraft fulfill a myriad of critical functions on orbit, from defense and intelligence to science, navigation, and telecommunication. Spacecraft can also cost several hundred millions of dollars to design and launch, and given that physical access for maintenance remains difficult if not impossible to date, designing high reliability and survivability into these systems is an engineering and financial imperative. While reliability is recognized as an essential attribute for spacecraft, little analysis has been done pertaining to actual field reliability of spacecraft and their subsystems. This thesis consists of two parts. The first part fills the gap in the current understanding of spacecraft failure behavior on orbit through extensive statistical analysis and modeling of anomaly and failure data of Earth-orbiting spacecraft. The second part builds on these results to develop a novel theoretical basis (interdependent multi-layer network approach) and algorithmic tools for the analysis of survivability of spacecraft and space-based networks. Space-based networks (SBNs) allow the sharing of on-orbit resources, such as data storage, processing, and downlink. Results indicate and quantify the incremental survivability improvement of the SBN over the traditional monolith architecture. A trade-space analysis is then conducted using non-descriptive networkable subsystems/technologies to explore survivability characteristics of space-based networks and help guide design choices.