PIM proteins, which are proto-oncogenic serine/threonine kinases that are highly expressed in hematological malignancies and solid cancers, are potential molecular targets for anticancer drugs. 1H-Benzo[d]imidazol-2(3H)-one is a key structure in drug discovery, and several of its analogues have been developed as therapeutics. 1,6-Disubstituted-1H-benzo[d]imidazol-2(3H)-one derivatives were synthesized and evaluated in terms of their inhibitory activities against all three PIM kinases. Systematic structural modifications of benzo[d]imidazol-2-one at the 1- and 6-positions led to the discovery of pan-PIM inhibitors represented by 9. The binding modes of the synthesized compounds and the effects of the substituents on the selectivities among the PIM kinase isoforms were studied to confirm 1,6-disubstituted-1H-benzo[d]imidazol-2(3H)-one as a scaffold for use in the discovery of PIM kinase inhibitors.