Aim To determine whether repeated maximal‐intensity hypoxic exercise induces larger beneficial adaptations on the hypoxia‐inducible factor‐1α pathway and its target genes than similar normoxic exercise, when combined with chronic hypoxic exposure. Methods Lowland elite male team‐sport athletes underwent 14 days of passive normobaric hypoxic exposure [≥14 h·day−1 at inspired oxygen fraction (FiO2) 14.5–14.2%] with the addition of six maximal‐intensity exercise sessions either in normobaric hypoxia (FiO2 ~14.2%; LHTLH; n = 9) or in normoxia (FiO2 20.9%; LHTL; n = 11). A group living in normoxia with no additional maximal‐intensity exercise (LLTL; n = 10) served as control. Before (Pre), immediately after (Post‐1) and 3 weeks after (Post‐2) the intervention, muscle biopsies were obtained from the vastus lateralis. Results Hypoxia‐inducible factor‐1α subunit, vascular endothelial growth factor, myoglobin, peroxisome proliferator‐activated receptor‐gamma coactivator 1‐α and mitochondrial transcription factor A mRNA levels increased at Post‐1 (all P ≤ 0.05) in LHTLH, but not in LHTL or LLTL, and returned near baseline levels at Post‐2. The protein expression of citrate synthase increased in LHTLH (P < 0.001 and P < 0.01 at Post‐1 and Post‐2, respectively) and LLTL (P < 0.01 and P < 0.05 at Post‐1 and Post‐2, respectively), whereas it decreased in LHTL at Post‐1 and Post‐2 (both P < 0.001). Conclusion Combined with residence in normobaric hypoxia, repeated maximal‐intensity hypoxic exercise induces short‐term post‐intervention beneficial changes in muscle transcriptional factors that are of larger magnitude (or not observed) than with similar normoxic exercise. The decay of molecular adaptations was relatively fast, with most of benefits already absent 3 weeks post‐intervention.