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An approach for modeling topologically interlocked building blocks that can be assembled in a water‐tight manner (space filling) to design a variety of spatial structures is introduced. This approach takes inspiration from recent methods utilizing Voronoi tessellation of spatial domains using symmetrically arranged Voronoi sites. Attention is focused on building blocks that result from helical stacking of planar 2‐honeycombs (i.e., tessellations of the plane with a single prototile) generated through a combination of wallpaper symmetries and Voronoi tessellation. This unique combination gives rise to structures that are both space‐filling (due to Voronoi tessellation) and interlocking (due to helical trajectories). Algorithms are developed to generate two different varieties of helical building blocks, namely, corrugated and smooth. These varieties result naturally from the method of discretization and shape generation and lead to distinct interlocking behavior. In order to study these varieties, finite‐element analyses (FEA) are conducted on different tiles parametrized by 1) the polygonal unit cell determined by the wallpaper symmetry and 2) the parameters of the helical line generating the Voronoi tessellation. Analyses reveal that the new design of the geometry of the building blocks enables strong variation of the engagement force between the blocks.