The retrieval of concepts from semantic memory is fundamental to higher-order cognitive functions and complex behaviors. Despite its vulnerability to disruption-particularly from irrelevant auditory stimuli with semantic content-the mechanisms through which such distractors hinder coherent semantic processing and retrieval remain poorly understood. To address this issue, we conducted four experiments using a novel retrieval interference paradigm, manipulating both the demands on semantic search and retrieval (automatic-associative vs. controlled-dissociative) and the type of distractor (acoustic-meaningless vs. semantic-meaningful, prepotent or remote). Our results show that meaningful distractors significantly disrupt semantic memory retrieval, especially under controlled retrieval demands, while acoustic distractors have minimal impact. Through examining task difficulty, interference habituation, and working memory capacity, we provide converging evidence that the disruption was primarily driven by an interference-by-process mechanism, wherein incidental distractor processing evokes task-irrelevant activation within the semantic network. Moreover, interference was stronger when distractors were semantically close to the retrieval cue, indicating that difficulty in suppressing prepotent, cue-related activations contributes to retrieval disruption. Based on these findings, we propose an activation-suppression framework, whereby semantic interference arises from the interplay between automatic spreading activation and the need for inhibitory control to suppress task-incongruent conceptual activations. These results refine our understanding of the mechanisms underlying semantic retrieval and highlight the putative role of cognitive control in managing semantic distraction.