Automotive accidents and subsequent personal injury claims incur substantial costs annually. While seat and head restraint design continue to evolve and improve, occupant safety and injury risk assessment in rear-end collisions remain at the forefront of automotive innovation. In this study, we combined statistical analyses of nine years (2007-2015) of data from the National Automotive Sampling System Crashworthiness Data System (NASS-CDS) database and one year (2017) of data from the Crash Investigation Sampling System (CISS) database with data acquired from vehicle-to-vehicle crash tests conducted with instrumented anthropomorphic test device (ATD) occupants. Together, these analyses were used to compare and relate field injury rates with potential mechanisms underlying head, cervical spine, lumbar spine, and lower extremity injuries in low-to moderate-speed rear-end collisions. First, we performed statistical analyses of the NASS-CDS and CISS databases to estimate the rate of AIS 2+ and AIS 3+ cervical spine, lumbar spine, and lower extremity injuries, as well as a subset of AIS 2+ and AIS 3+ internal head injuries, including recorded unconsciousness and concussion. The results of these analyses were then compared to measured occupant loading data from rear-end crash tests performed at delta-Vs ranging from 5.6 to 19.5 km/h, using restrained, nominally positioned, and instrumented Hybrid III 50th percentile male ATDs. Kinematic and kinetic data for the head, cervical spine, lumbar spine, and lower extremities collected in the low- to moderate-speed rear-end crash tests were well below injury thresholds. Analysis of the NASS-CDS and CISS databases demonstrated low rates of injury to the head, cervical spine, lumbar spine, and lower extremities in low- to moderate-speed rear-end collisions. Review of these rear-end crashes revealed that, outside of collision speed and crash severity, potential muscle activation, occupant age, and occupant compartment configuration may play a role in increasing the likelihood of injury.