Soft robots are ideal to interact safely alongside humans when compared to rigid‐bodied robots. These robots require robust soft sensors that can sustain large deformations. Novel soft pneumatic sensing chambers (SPSCs) that can be directly 3D printed using a low‐cost 3D printer and an off‐the‐shelf thermoplastic poly(urethane) (TPU) are presented. The SPSCs are responsive to four main mechanical input modalities of compression, bending, torsion, and rectilinear displacement, and all of these cause a pressure change in the SPSCs. The SPSCs have several advantages including fast response, linearity, negligible hysteresis, repeatability and reliability, stability over time, long lifetime, and very low power consumption. The SPSCs are optimized using finite element modeling (FEM) simulations to obtain a linear relationship between the input mechanical modalities and the output pressure. With the hyperelastic material model developed for the TPU, the FEM simulations accurately predict the experimental behavior. These SPSCs are generic and can be tailored to diverse soft and interactive human–machine interfaces including soft wearable gloves for virtual reality applications and soft adaptive grippers control, soft push buttons for science, technology, engineering, and mathematics (STEM) education platforms, haptic feedback devices for rehabilitation, soft game controllers and soft throttle controllers for gaming, and soft bending sensors for soft prosthetic hands.