The research described in this article aims to prepare for vehicles equipped with advanced automation technology. To better understand the effects of reclined and rotated seating positions in the full-frontal impact condition, a simulation study was conducted using a validated generic sled model with interior, deformable seat, realistic package, and restraints. Two state-of-the-art anthropomorphic test devices (ATDs), Hybrid 3 and THOR, and two human body models (HBM), Global Human Body Model (GHBM) and Total HUman Model for Safety (THUMS), were used to evaluate differences in occupant kinematics and injury risk for different seatback recline angles and seating orientations. The effect of a 45-degree reclined versus a 23-degree nominal seatback angle at six different seating orientations, i.e., 11:30, 12, and 12:30 clock-face front-facing and 5:30, 6, and 6:30 clock-face rear-facing, was studied. Two approaches were used to assess injury risk: (1) injury risk based on accelerometer, potentiometer, and force transducer instrumentation data and (2) strain-based injury risk assessment for HBMs. The probabilities of Abbreviated Injury Scale (AIS) 3+ injuries were calculated using respective risk functions for relevant body regions and were combined into a joint injury risk. It was found that seating posture and orientation have a significant effect on occupant kinematics and loads. For example, (1) AIS 3+ injury risk increased by 28% for the 12 o’clock compared to the 12:30 clock-face rotated front-facing seating orientation and (2) AIS 3+ injury risk decreased by 25% for the 45-degree reclined 6 o’clock compared to the 23-degree nominal 6 o’clock rear-facing postures. Although existing occupant models have undergone limited validation for rear-facing scenarios, they were considered adequate for the purpose of this research. In conclusion, this study quantifies the effect of reclined and rotated seating postures in full-frontal crash scenarios. Recommended future research includes the use of further enhanced occupant models and the analysis of restraints that are tailored for automated vehicle (AV) concepts.