In this paper, we introduce 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. Our approach takes inspiration from recent methods utilizing Voronoi tessellation of spatial domains using symmetrically arranged Voronoi sites. We specifically focus our attention 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 (owing to Voronoi tessellation) and interlocking (owing to helical trajectories). We develop algorithms 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, we conduct finite element analyses on different families of helical blocks parametrized by: (a) the polygonal unit cell as determined by the wallpaper symmetry and (b) the parameters of the helical line generating the Voronoi tessellation, i.e., the radius and pitch of the helix. Our analyses revealed that the new design of the geometry of the building blocks enables strong variation of the engagement force between the blocks.This article is protected by copyright. All rights reserved.