Over the past five decades, marine mammal interactions with fisheries have become a major human-wildlife conflict globally. The emergence of longline fishing is concomitant with the development of depredation-type interactions i.e., marine mammals feeding on fish caught on hooks. The killer whale (Orcinus orca) is one of the species most involved in depredation on longline fisheries. The issue was first reported in high latitudes but, with increasing expansion of this fishing method, other fisheries have begun to experience interactions. The present study investigated killer whale interactions with two geographically isolated blue-eye trevalla (Hyperoglyphe antarctica) fisheries operating in temperate waters off Amsterdam/St. Paul Islands (Indian Ocean) and south-eastern Australia. These two fisheries differ in the fishing technique used (vertical vs. demersal longlines), effort, catch, fleet size and fishing area size. Using 7-year (2010–16) long fishing and observation datasets, this study estimated the levels of killer whale interactions and examined the influence of spatio-temporal and operational variables on the probability of vessels to experience interactions. Killer whales interactions occurred during 58.4% and 21.2% of all fishing days, and over 94% and 47.4% of the fishing area for both fisheries, respectively. In south-eastern Australia, the probability of occurrence of killer whale interactions during fishing days varied seasonally with a decrease in spring, increased with the daily fishing effort and decreased with the distance travelled by the vessel between fishing days. In Amsterdam/St. Paul, this probability was only influenced by latitude, with an increase in the southern part of the area. Together, these findings document two previously unreported cases of high killer whale depredation, and provide insights on ways to avoid the issue. The study also emphasizes the need to further examine the local characteristics of fisheries and the ecology of local depredating killer whale populations in as important drivers of depredation.