Fly-in fly-out work patterns have become an integral part of employment in the Australian resource sector. When attachment to parents is disrupted by a parent working away from home on a regular basis, young people’s feelings of connection to their family may be impacted, as well as their mental and emotional well-being compromised. The objective of this study was to explore the mediation of parental presence and family connectedness on the association between fly-in fly-out employment and adolescent well-being. A cross-sectional survey of over 3,000 Grades 5–10 students from 40 Perth West Australian metropolitan and rural schools identified 618 students whose parents were involved in fly-in fly-out employment. Multi-level mediation analysis showed that the negative relationship between fly-in fly-out status and adolescent depressive symptoms and emotional and behavioural difficulties was fully or partially mediated by parent presence and family connectedness, controlling for both student and school level demographics. The intermittent absence/presence of fly-in fly-out employment patterns appears to create challenges for workers and their families, not experienced by non-fly-in fly-out families.This study highlights the importance of strengthening family connections within fly-in fly-out households. Suggestions have been made to help fly-in fly-out parents to stay in touch with their families.