A nationwide invasive pneumococcal disease (IPD) outbreak caused by the previously rare Streptococcus pneumoniae serotype 2 (Sp2) was observed during 2014-2017 in Israel. We aimed to characterize the population structure and evolutionary dynamics of Sp2 during 2009-2017. A nationwide, active surveillance is being conducted since 2009. Serotype Sp2 was determined by PCR and Quellung reaction. Selected Sp2 isolates from IPD cases during 2009-2017 were analyzed by PFGE, MLST and whole genome sequencing (WGS). Antimicrobial profiling was performed by broth micro-dilution. Overall, 103 Sp2 IPD cases were identified (July 2009 through June 2017); 80 (77.7%) isolates were analyzed by PFGE and 49 (47.8%) isolates were analyzed by MLST. Selected isolates were also analyzed by WGS. During 2016-2017, Sp2 caused 7.8% of all-IPD, a 7-fold increase compared with 2009-2010, and ranked third among the IPD isolates. During 2009-2014, all sequenced Sp2 IPD were caused by the globally reported ST-1504 clone (pubMLST). The predominant outbreak strain among 2015-2017 isolates was ST-13578, not previously observed worldwide before 2015. Whole genome SNPs analysis confirmed that ST-13578 isolates were clonal (≤6 SNPs) and genetically distinct from ST-1504 (356 SNPs). High ratio of SNPs was detected in two main regions of ST-13578 genomes indicative of recombination events. All tested strains were penicillin-susceptible (MIC