The Southern Ocean is an important region of ocean carbon uptake, and observations indicate its air-sea carbon flux fluctuates from seasonal to decadal timescales. Carbon fluxes at regional scales remain highly uncertain due to sparse observation and intrinsic complexity of the biogeochemical processes. The objective of this study is to better understand the mechanisms influencing variability of carbon uptake in the Drake Passage. A regional circulation and biogeochemistry model is configured at the lateral resolution of 10 km, which resolves larger mesoscale eddies where the typical Rossby deformation radius is (50 km). We use this model to examine the interplay between mean and eddy advection, convective mixing, and biological carbon export that determines the surface dissolved inorganic carbon and partial pressure of carbon dioxide variability. Results are validated against in situ observations, demonstrating that the model captures general features of observed seasonal to interannual variability. The model reproduces the two major fronts: Polar Front (PF) and Subantarctic Front (SAF), with locally elevated level of eddy kinetic energy and lateral eddy carbon flux, which play prominent roles in setting the spatial pattern, mean state and variability of the regional carbon budget. The uptake of atmospheric CO 2 , vertical entrainment during cool seasons, and mean advection are the major carbon sources in the upper 200 m of the region. These sources are balanced by the biological carbon export during warm seasons and mesoscale eddy transfer. Comparing the induced advective carbon fluxes, mean flow dominates in magnitude, however, the amplitude of variability is controlled by the eddy flux. Plain Language Summary The Southern Ocean, which surrounds Antarctica, is a critical component of global climate and carbon cycling. The Drake Passage is the region south of the tip of South America. It is one of the most well sampled sectors of the Southern Ocean, and the narrowest and southernmost constriction of the Antarctic Circumpolar Current. While the region is an overall carbon sink, its carbon uptake can fluctuate over time, and its uncertainty comes from sparse observations and the complex nature of the contributing processes. We use a regional ocean circulation and biogeochemical model to better understand the influencing mechanisms on the variability of carbon uptake to the region. Model results demonstrate that absorbed atmospheric carbon, strong wintertime mixing and vertical water movement, and mean ocean currents are the major source of carbon in the upper 200 m of the Drake Passage. These inputs of carbon into the ocean are balanced by smaller scale (10-100 km) movements called ocean eddies and the biological drawdown of carbon. This research allows for better comprehension of regional carbon fluxes and analysis of biophysical dynamics influencing the annual and interannual fluctuation.