Anthropogenic manipulation of sub-surface fluids associated with hydrocarbon, groundwater, and geothermal resource extraction can result in displacement of the Earth's crust and changes in seismicity rates. This has implications for seismic hazards, as well as environmental impacts associated with the deformation itself (e.g., flooding, structural damage, etc.) and the depletion of resources and reservoir storage. In this dissertation, I focus on approaches for improving measurements of natural and anthropogenic deformation using space-based geodesy. Space-based geodetic methods, including Interferometric Synthetic Aperture Radar (InSAR) and continuous Global Navigation Satellite System (GNSS), provide observations of active deformation of the Earth's crust over time scales ranging from days to decades. These methods allow us to monitor the effects of natural and anthropogenic processes, as well as begin to understand how the associated deformation may affect the state of stress around nearby faults and potentially lead to change in seismicity rates. However, both the precision and accuracy of InSAR are limited over much of the Earth's surface because of noise from sources such as variations in ground surface properties and tropospheric and ionospheric variability. Because of this, there are almost certainly areas where we are not yet aware of the extent to which anthropogenic activities are causing crustal deformation, and we are not able to monitor these areas nor leverage them for scientific inquiry. Here, I explore methods to address these noise sources, including data processing techniques that improve InSAR data quality, and new methods for mitigating noise from tropospheric variability over time. I show how these methods can enhance our ability to constrain deformation in challenging areas such as the Central United States and south-central Mexico. I provide analyses of geodetic datasets that illuminate the response of aquifers in California's Central Valley to variations in usage and drought severity. This includes consideration of spatio-temporal variability of crustal deformation as California recovered from a severe drought in 2017. Finally, I explore techniques for inverting multiple one-dimensional InSAR observations to recover a three-dimensional deformation field. I use these improved 3-D constraints to measure strain near the Garnet Hill fault in California's Coachella Valley, a region within a few kilometers of the southern San Andreas fault. I show that this fault was likely driven closer to failure as a result of a period of enhanced activity at a nearby groundwater entrainment facility.