Seed germination is a crucial checkpoint for plant survival under unfavorable environmental conditions. Abscisic acid (ABA) and its signaling play a vital role in integrating environmental information to regulate seed germination. MCM1/AGAMOUS/DEFICIENS/SRF (MADS)-box transcription factors are mainly known as key regulators of seed and flower development in Arabidopsis. However, their functions in seed germination are still poorly understood. Here we report that MADS-box transcription factor AGL21 negatively modulates seed germination and post-germination growth by controlling the expression of ABA-INSENSITIVE 5 (ABI5) in Arabidopsis. AGL21 responds to multiple environmental stresses and plant hormones. The AGL21-overexpressing plants are hypersensitive to ABA, salt and osmotic stresses during seed germination and early post-germination growth, whereas agl21 mutants are less sensitive. AGL21 positively regulates ABI5 expression in seeds. Genetic analyses reveal that AGL21 is epistatic to ABI5 in controlling seed germination. Chromatin immunoprecipitation assays further demonstrate that AGL21 could directly bind to the ABI5 promoter in plant cells. Taken together, our results suggest that AGL21 acts as a surveillance integrator that incorporates environmental cues and endogenous hormonal signals into ABA signaling to regulate seed germination and early post-germination growth.