The engineering of highly active, stable, and inexpensive catalysts for CO oxidation reaction through the modulations of morphology and structure is desirable but remains a great challenge. Herein, we reported the rational design of novel hollow‐Co3O4@Co3O4@SiO2 multi‐yolk‐double‐shell nanoreactors by using a two‐step annealing recipe employing core‐shelled ZIF‐67@SiO2 as a precursor. The unique structures of the multi‐yolk‐double‐shell and hollow interior of Co3O4 endowed the materials with promising properties of sufficient active interfacial sites, porous structures, efficient oxygen delivery capacity, and more oxygen vacancies, which were beneficial for CO oxidation. Consequently, the H−Co3O4@Co3O4@SiO2(35)‐250 nanoreactor exhibited outstanding catalytic performance, achieving complete CO conversion at 100 °C, which was far exceeding that of hollow Co3O4 NPs derived from pure ZIF‐67 and also solid Co3O4@SiO2(35)‐250 with a complete conversion of CO at 190 and 230 °C, respectively, and even outperformed most of the reported Co3O4‐based catalysts. Moreover, H−Co3O4@Co3O4@SiO2(35)‐250 could continuously work for 28 h without any deactivation and maintain 93 % CO conversion within 34 h at 100 °C. The proposed strategy of designing and fabricating novel structures offers great opportunities in developing highly active hollow metal oxide‐based nanoreactors for a variety of advanced applications.