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Translation initiation in eukaryotes requires multiple eukaryotic translation initiation factors (eIFs) and involves continuous remodeling of the ribosomal preinitiation complex (PIC). The GTPase eIF2 brings the initiator Met‐tRNAi to the PIC. Upon start codon selection and GTP hydrolysis promoted by its GTPase‐activating protein (GAP) eIF5, eIF2‐GDP is released in complex with eIF5. It is not known how eIF5 dissociates from its other binding partners to leave the PIC with only eIF2. Here, we report that two intrinsically disordered regions (IDRs) in eIF5, the DWEAR motif and the C‐terminal tail (CTT) dynamically contact the folded C‐terminal domain (CTD) and compete with each other. The eIF5‐CTD•CTT interaction shows modest synergy with eIF2β binding to eIF5‐CTD, whereas the eIF5‐CTD•DWEAR interaction favors eIF1A binding, instead. These findings allowed us to propose a model explaining how the rearrangement of the eIF5 intramolecular contacts can mediate remodeling of multiple interactions upon start codon selection. Using phosphomimetic mutations, we show that phosphorylation of eIF5 by Casein Kinase 2 (CK2) increases the affinity of eIF5 for eIF2β. Our results help elucidate the molecular mechanisms of stimulation of protein synthesis and cell proliferation by CK2.