Purpose: Exercise intensity during walking can be increased by attaching an external load or accelerating the walking speed. However, the combination of these effects on the human body remains unclear. To investigate the influence of different walking speeds and ankle weight loads on metabolic and neuromuscular responses and lower limb kinematics during walking. Methods: Twelve healthy participants walked on a treadmill under eight conditions (speed: 4 and 7 km/h × ankle weight loads: 0, 2, 4, and 6 kg). We recorded V ˙ O 2 , heart rate (HR), lower limb neuromuscular activities, and kinematic data. Results: The interaction effect of speed and ankle weight load on V ˙ O 2 and HR was significant (p < 0.05). V ˙ O 2 and HR were higher during walking at 7 than 4 km/h (p < 0.05). V ˙ O 2 rapidly rose with an increase in ankle weight loading from 4 to 6 kg during walking at 7 km/h compared with that at 4 km/h (p < 0.05). Rectus femoris proximal activity with 6 kg ankle weight loading was higher than that under the no-loading condition during walking at 7 km/h (p < 0.05). During walking at 4 km/h, medial gastrocnemius muscle activity with 4- and 6 kg ankle weight loading was significantly higher than under the no-loading condition (p < 0.05). All targeted lower limb muscle activity and the maximum hip flexion angle were greater during walking at 7 than 4 km/h. Conclusion: Our results suggest that the effect of ankle weight loading on metabolic and neuromuscular responses is potentiated by a faster walking speed. [ABSTRACT FROM AUTHOR]