Exercise enhances aspects of human cognition, but its intensity may matter. Recent animal research suggests that vigorous exercise, which releases greater amounts of lactate, activates more brain-derived neurotrophic factor (BDNF) in the hippocampus and, thus, may be optimal for supporting cognitive function. The cognitive benefits of exercise may be further augmented when combined with cognitive training. The sport of orienteering simultaneously combines exercise with spatial navigation and, therefore, may result in greater cognitive benefits than exercising only, especially at vigorous intensities. The present study aimed to examine the effects of an acute bout of orienteering at different intensities on cognition and BDNF compared to exercising only. We hypothesized that vigorous-intensity orienteering would increase lactate and BDNF and improve cognition more than moderate-intensity orienteering or vigorous exercise alone. Sixty-three recreationally active, healthy young adults (Mage = 21.10±2.75 years) with no orienteering experience completed a 1.3 km intervention course by navigating and exercising at a vigorous (80–85% of heart rate reserve) or moderate (40–50% of heart rate reserve) intensity or exercising vigorously without navigation. Exercise intensity was monitored using peak lactate, heart rate and rating of perceived exertion. Serum BDNF was extracted immediately before and after the intervention. Memory was assessed using the Mnemonic Similarity Task (high-interference memory) and the Groton Maze Learning Test (spatial memory). Both exercising and orienteering at a vigorous intensity elicited greater peak lactate and increases in BDNF than moderate-intensity orienteering, and individuals with higher peak lactate also had greater increases in BDNF. High-interference memory improved after both vigorous-intensity interventions but did not improve after the moderate-intensity intervention. Spatial memory only increased after vigorous-intensity orienteering, suggesting that orienteering at a vigorous intensity may particularly benefit spatial cognition. Overall, the results demonstrate the benefits of vigorous exercise on human cognition and BDNF.