Plant defense responses are tightly controlled by many positive and negative regulators to cope with attacks from various pathogens. Arabidopsis EDR2 (ENHANCED DISEASE RESISTANCE 2) is a negative regulator of powdery mildew resistance and edr2 mutants display enhanced resistance to powdery mildew (Golovinomyces cichoracearum). To identify components acting in the EDR2 pathway, we screened for edr2 suppressors and identified a gain-of-function mutation in SR1 (SIGNAL RESPONSIVE 1), which encodes a calmodulin-binding transcription activator. The sr1-4D gain-of-function mutation suppresses all edr2-associated phenotypes, including powdery mildew resistance, mildew-induced cell death and ethylene-induced senescence. The sr1-4D single mutant is more susceptible to a Pseudomonas syringae pv. tomato (Pto) DC3000 virulent strain and to avirulent strains carrying avrRpt2 or avrRPS4 than wild type. We show that SR1 directly binds to the promoter region of NDR1, a key component in RPS2-mediated plant immunity. Also, the ndr1 mutation suppresses the sr1-1 null allele, which shows enhanced resistance to both Pto DC3000 avrRpt2 and G. cichoracearum. In addition, we show that SR1 regulates ethylene-induced senescence by directly binding to the EIN3 promoter region in vivo. Enhanced ethylene-induced senescence in sr1-1 is suppressed by ein3. Our data indicate that SR1 plays an important role in plant immunity and ethylene signaling by directly regulating NDR1 and EIN3.