Research in human–computer interaction (HCI) has identified meaning as an important, yet poorly understood concept in interaction design contexts. Central to this development is the increasing emphasis on designing products and technologies that promote leisure, personal fulfillment, and well-being. As spaces of profound historical significance and societal value, museums offer a unique perspective on how people construct meaning during their interactions in museum spaces and with collections, which may help to deepen notions of the content of meaningful interaction and support innovative design for cultural heritage contexts. The present work reports on the results of two studies that investigate meaning-making in museums. The first is an experience narrative study (N = 32) that analyzed 175 memorable museum visits, resulting in the establishment of 23 triggers that inform meaningful interaction in museums. A second study (N = 354) validated the comprehensiveness and generalisability of the triggers by asking participants to apply them to their own memorable museum experiences. We conclude with a framework of meaning in museums featuring the 23 triggers and two descriptive categories of temporality and scope. Our findings contribute to meaning research in HCI for museums through an articulation of the content of meaning-making in the cultural sector.