In this work a multilayer barrier paperboard was produced in a roll-to-roll process by slot-die coating of nanocellulose (microfibrillated cellulose or carboxymethylated cellulose nanofibrils) followed by extrusion coating of biodegradable thermoplastics (polylactic acid, polybutylene adipate terephthalate and polybutylene succinate). Hyperplaty kaolin pigments were blended in different ratios into nanocellulose to tailor the barrier properties of the multilayer structure and to study their influence on adhesion to the thermoplastic top layer. Influence of a plasticizer (glycerol) on flexibility and barrier performance of the multilayer structure was also examined. Water vapor permeance for the multilayer paperboard was below that of control single-layer thermoplastic materials, and oxygen permeance of the coated structure was similar or lower than that of pure nanocellulose films. Glycerol as a plasticizer further lowered the oxygen permeance and kaolin addition improved the adhesion at the nanocellulose/thermoplastic interface. The results provide insight into the role played by nanocelluloses, thermoplastics, pigments, and plasticizers on the barrier properties when these elements are processed together into multilayer structures, and paves the way for industrial production of sustainable packaging.