Environmental problems associated with the growing levels of carbon dioxide in the atmosphere due to the burning of fossil fuels to satisfy the high demand for energy are a pressing concern. Therefore, the design of new materials for carbon dioxide storage has received increasing research attention. In this work, we report the synthesis of three new Schiff bases containing a trimethoprim unit and the investigation of their application as adsorbents for carbon dioxide capture. The reaction of trimethoprim and aromatic aldehydes in acid medium gave the corresponding Schiff bases in 83%−87% yields. The Schiff bases exhibited surface areas ranging from 4.15 to 20.33 m2/g, pore volumes of 0.0036−0.0086 cm3/g, and average pore diameters of 6.64−1.4 nm. An excellent carbon dioxide uptake (27−46 wt%) was achieved at high temperature and pressure (313 K and 40 bar, respectively) using the Schiff bases. The 3-hydroxyphenyl-substituted Schiff base, which exhibited a meta-arrangement, provided the highest carbon dioxide uptake (46 wt%) due to its higher surface area, pore volume, and pore diameter compared with the other two derivatives with a para-arrangement.