Oxygen (O2) availability is essential for healthy coral reef functioning, yet how continued loss of dissolved O2 via ocean deoxygenation impacts performance of reef building corals remains unclear. Here, we examine how intra-colony spatial geometry of important Great Barrier Reef (GBR) coral species Acropora may influence variation in hypoxic thresholds for upregulation, to better understand capacity to tolerate future reductions in O2 availability. We first evaluate the application of more streamlined models used to parameterise Hypoxia Response Curve data, models that have been used historically to identify variable oxyregulatory capacity. Using closed-system respirometry to analyse O2 drawdown rate, we show that a two-parameter model returns similar outputs as previous 12th-order models for descriptive statistics such as the average oxyregulation capacity (Tpos) and the ambient O2 level at which the coral exerts maximum regulation effort (Pcmax), for diverse Acropora species. Following an experiment to evaluate whether stress induced by coral fragmentation for respirometry affected O2 drawdown rate, we subsequently identify differences in hypoxic response for the interior and exterior colony locations for the species Acropora abrotanoides, Acropora cf. microphthalma and Acropora elseyi. Average regulation capacity across species was greater (0.78–1.03 ± SE 0.08) at the colony interior compared with exterior (0.60–0.85 ± SE 0.08). Moreover, Pcmax occurred at relatively low pO2 of <30% (±1.24; SE) air saturation for all species, across the colony. When compared against ambient O2 availability, these factors corresponded to differences in mean intra-colony oxyregulation, suggesting that lower variation in dissolved O2 corresponds with higher capacity for oxyregulation. Collectively, our data show that intra-colony spatial variation affects coral oxyregulation hypoxic thresholds, potentially driving differences in Acropora oxyregulatory capacity.