Exposure to early-life antibiotics (ELA) promotes adult obesity across diverse species, an effect often stronger in males than females. However, the physiological and evolutionary mechanisms driving ELA-mediated developmental responses and their consequences for host fitness remain unclear. Here, treating young mice with pulsed high-dose (therapeutic) or chronic low-dose (subtherapeutic) ampicillin elicited reduced lean mass and energy expenditure in males that promoted increased visceral adiposity in adulthood, despite differing impacts on the gut microbiota across treatments. High-dose but not low-dose ELA also temporarily reduced host growth and short-chain fatty acid production during treatment, raising the possibility that the developmental response to high-dose ELA could be considered an adaptive response to an energy-limited environment. We therefore assessed markers of metabolic, reproductive, and immune fitness in adulthood under caloric restriction or free-fed conditions. Although high-dose ELA-treated males had reduced fitness under free-fed conditions—driven by smaller body size, fat stores, and impaired immunity—they were buffered against additional fitness reductions under caloric restriction, consistent with predictive adaptive response models of development. Strikingly, high-dose ELA-treated females exhibited none of the proximate metabolic responses observed in males, with adult body size and composition remaining indistinguishable from controls. In the absence of similar developmental plasticity, females exhibited exacerbated fitness reductions under caloric restriction, including reduced energetic investments in reproduction and immunity. Our results suggest that antibiotic exposures can elicit characteristics of negative energy balance when administered at dosages that disrupt gut microbial contributions to host energy gain. Such microbiota disruption during early life can subsequently induce sexually dimorphic developmental responses with consequences for long-term health and adult fitness.