There is an increased interest in the use of cellulose nanocrystal (CNC) films and coatings for a range of functional applications in the fields of material science, biomedical engineering, and pharmaceutical sciences. Most of these applications have been demonstrated on films and coatings produced using laboratory-scale batch processes, such as solvent casting, dip coating, or spin coating. For successful coating application of CNC suspensions using a high throughput process, several challenges need to be addressed: relatively high viscosity at low solids content, coating brittleness, and potentially poor adhesion to the substrate. This work aims to address these problems. The impact of plasticizer on suspension rheology, coating adhesion, and barrier properties was quantified, and the effect of different pre-coatings on the wettability and adhesion of CNC coatings to paperboard substrates was explored. CNC suspensions were coated onto pre-coated paperboard in a roll-to-roll process using a custom-built slot die. The addition of sorbitol reduced the brittleness of the CNC coatings, and a thin cationic starch pre-coating improved their adhesion to the paperboard. The final coat weight, dry coating thickness, and coating line speed were varied between 1–11 g/m2, 900 nm–7 µm, and 2.5–10 m/min, respectively. The barrier properties, adhesive strength, coating coverage, and smoothness of the CNC coatings were characterized. SEM images show full coating coverage at coat weights as low as 1.5 g/m2. With sorbitol as plasticizer and at coat weights above 3.5 g/m2, heptane vapor and water vapor transmission rates were reduced by as much as 99% and 75% respectively. Compared to other film casting techniques, the process employed in this work deposits a relatively thick coating in significantly less time, and may therefore pave the way toward various functional applications based on CNCs.