Chromosomal rearrangements can be oncogenic driver events in cancers. In contrast to hematological malignancies where chromosomal rearrangements are often initiated by the activation-induced cytidine deaminase (AID) enzyme, the mechanisms that induce rearrangements in solid cancers remain largely unknown. Here, we tested the activity of each of the 7 members of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3; A3) family enzymes with genome-wide rearrangement assays. We discovered that A3 enzymes induced focal clusters of rearrangements (FCRs) and dispersed clusters of rearrangements (DCRs). While AID-induced FCRs were enriched near transcription start sites (TSS) and within gene bodies, A3-induced FCRs were mainly located within gene bodies with limited activity at the TSS. AID- and A3-induced rearrangements primarily occurred in early replication timing regions, A compartments, and topologically associated domain boundaries. A3A showed superior activity to induce chromosomal rearrangements and mutations near breakpoints compared to other A3 family members. Remarkably, A3s promoted the formation of oncogenic tyrosine kinase (TK) fusions in lung cancer models in vitro and in vivo . Thus, A3 enzymes induce chromosomal rearrangements by recurrent patterns and enhance the formation of oncogenic fusions in cancers.