Stabilisation of proximal humerus fractures remains a surgical challenge. Spatial subchondral support (S3) plate promises to overcome common complications associated with conventional proximal humerus plates. This study compared the biomechanical performance of S3 plate with a fixed-angle hybrid blade (Equinoxe Fx) plate and a conventional fixed-angle locking plate (PHILOS). The effects of removal of different S3 plate screws on the humeral stability were also investigated. A total of 20 synthetic left humeri were osteotomised transversely at the surgical neck to simulate a two-part fracture and were each treated with an S3 plate. Head screws were divided into three zones based on their distance from the fracture site. Specimens were divided into four equal groups where one group acted as a control with all screws and three groups had one of the screw zones missing. With humeral head fixed, humeral shaft was first displaced 5 mm in extension, flexion, valgus and varus direction (elastic testing) and then until 30 mm varus displacement (plastic testing). Load–displacement data were recorded to determine construct stiffness in elastic tests and assess specimens’ varus stability under plastic testing. Removal of the screw nearest to the fracture site led to a 20.71% drop in mean elastic varus bending stiffness. Removal of the two inferomedial screw above it resulted in a larger drop. The proximal screw pair had the largest contribution to extension and flexion bending stiffness. Varus stiffness of S3 plate constructs was higher than PHILOS and Fx plate constructs. Stability of humeri treated with S3 plate depends on screws’ number, orientation and location. Varus stiffness of S3 plate construct (10.54 N/mm) was higher than that of PHILOS (6.61 N/mm) and Fx (7.59 N/mm) plate constructs. We attribute this to S3 plates’ thicker cross section, the 135° inclination of its screws with respect to the humeral shaft and the availability of pegs for subchondral support.