Coxiella burnetii modulates a variety of host cell processes to create a niche permissive for its intracellular replication using effectors injected by its Dot/Icm type Ⅳ secretion system. More than 130 such effectors have been identified, but the function of most of them remains unknown. Using an activity‐based screening strategy, we identified the C. burnetii protein CubL1 (Cbu0295) as an E3 ubiquitin ligase. Further analysis reveals that CubL1 catalyzes ubiquitination of eIF3g, a dual‐function protein involved in apoptosis and protein translation initiation. CubL1‐induced monoubiquitination inhibits the nuclease activity of eIF3g, essential for its role in cell death execution. Host cells infected by a C. burnetii mutant lacking cubL1 became more susceptible to cell death induction. Thus, C. burnetii employs multiple distinct mechanisms to maintain host cell viability to ensure successful completion of its intracellular life cycle.