Like in other eukaryotic cells, plant membrane trafficking pathways transport proteins among organelles and play essential roles in growth and development. The cargo proteins for membrane trafficking have diverse functions such as cell wall biosynthesis, signaling, and nutrient uptake. How plant cells accurately control protein transport in a spatiotemporal manner has not been well characterized. Cellulose synthase complexes (CSCs) are large membrane-associated protein complexes that catalyze the synthesis of cellulose at the plasma membrane. CSCs are delivered to the plasma membrane through membrane trafficking pathways for their proper functions. Using chemical genetic approach, we identified a small molecule that targets the catalytic domain of plant cellulose synthases. Combining small molecule treatment, live cell imaging and quantitative image analysis, we found that the catalytic activity of CSCs affected efficient exocytic transport of these large protein complexes. Inhibition of CSCs catalytic activity reduced the transport of CSCs at early steps of exocytic trafficking, although these protein complexes might have been assembled properly. Our results add to current understanding of how plant membrane trafficking machineries regulate spatiotemporal delivery of proteins for plant growth and environment adaptation.