Crotonyl-CoA carboxylase/reductase (Ccr) is one of the fastest CO2 fixing enzymes and has become part of efficient artificial CO2-fixation pathways in vitro, paving the way for future applications. The underlying mechanism of its efficiency, however, is not yet completely understood. X-ray structures of different intermediates in the catalytic cycle reveal tetramers in a dimer of dimers configuration with two open and two closed active sites. Upon binding a substrate, this active site changes its conformation from the open state to the closed state. It is challenging to predict how these coupled conformational changes will alter the CO2 binding affinity to the reaction's active site. To determine whether the open or closed conformations of Ccr affect binding of CO2 to the active site, we performed all-atom molecular simulations of the various conformations of Ccr. The open conformation without a substrate showed the highest binding affinity. The CO2 binding sites are located near the catalytic relevant Asn81 and His365 residues and in an optimal position for CO2 fixation. Furthermore, they are unaffected by substrate binding, and CO2 molecules stay in these binding sites for a longer time. Longer times at these reactive binding sites facilitate CO2 fixation through the nucleophilic attack of the reactive enolate in the closed conformation. We previously demonstrated that the Asn81Leu variant cannot fix CO2. Simulations of the Asn81Leu variant explain the loss of activity through the removal of the Asn81 and His365 binding sites. Overall, our findings show that the conformational dynamics of the enzyme controls CO2 binding. Conformational changes in Ccr increase the level of CO2 in the open subunit before the substrate is bound, the active site closes, and the reaction starts. The full catalytic Ccr cycle alternates among CO2 addition, conformational change, and chemical reaction in the four subunits of the tetramer coordinated by communication between the two dimers.