The diazabicyclooctane (DBO) inhibitor, avibactam (AVI), reversibly inactivates most serine-β-lactamases including the CTX-M β-lactamases. Currently, more than 230 CTX-M unique members distributed in five clusters with less than 5% amino acid sequence divergence within each group are described. Recently, a variant named as CTX-M-151 was isolated from a Salmonella Choleraesuis strain in Japan. This variant possesses a low degree amino acid identity with the other CTX-Ms (63.2-69.7% with respect to the mature proteins), and thus it may represent a new sub-group within the family. CTX-M-151 hydrolyzes ceftriaxone better than ceftazidime (kcat/Km values 6,000-fold higher), as observed with CTX-Ms. CTX-M-151 is well inhibited by mechanism-based inhibitors like clavulanic acid (kinact/KI = 0.15 μM−1.s−1). For AVI, Ki app (0.4 μM) was comparable to KPC-2; k2/K (37,000 M−1s−1) was lower than for CTX-M-15, while the koff (0.0015 s−1) was 2-14-fold faster than other class A β-lactamases. The structure of the CTX-M-151/AVI complex (1.32 Å) reveals that AVI adopts a chair conformation with hydrogen bonds between the AVI carbamate and Ser70 and Ser237 at the oxyanion hole. Upon acylation, the side chain of Lys73 points towards Ser130 which is associated with the protonation of Glu166, supporting the role of Lys73 in the proton-relay pathway and Glu166 as the general base in deacylation. To our knowledge, this is the first chromosomally-encoded CTX-M in Salmonella Choleraesuis that shows similar hydrolytic preference towards cefotaxime/ceftriaxone when compared to ceftazidime.