A fundamental question in modern-day ecology is: How will populations and their interactions respond to a rapidly changing climate? Documenting local collapses of ecologically and economically important populations can offer insight into broader patterns of decline. Here, we monitored anemonefish (Amphiprion bicinctus) and their host sea anemones (Radianthus magnifica) on three central Saudi Arabian Red Sea reefs from 2022 to 2024, including a 2023 marine heatwave that peaked at a Degree Heating Weeks (DHW) value of ~22 °C-weeks. Across all reefs, we observed a sequence of 100% anemone bleaching, 94.3–100% anemonefish mortality, and 66.4–94.1% anemone mortality. We compare these findings to other recent Indo-Pacific heat stress events of varying intensity, where similar declines were not observed. Our study highlights the vulnerability of mutualistic reef species to extreme heat and suggests that such events may drive local, if not regional, extinctions of ecologically important symbioses.