Acute changes in muscle architecture influenced by muscle swelling might be associated with chronic adaptations to resistance exercise, including skeletal muscle growth. Concentric (CON) and eccentric (ECC) muscle actions both play a role in hypertrophic processes, but the influence of each on acute indices of muscle swelling (i.e., muscle thickness (MT) and pennation angle (PA)) remains relatively unknown. Therefore, this study compared the acute changes in MT and PA in response to work-matched CON versus ECC isokinetic exercise. Twelve university-aged students performed 2 bouts of maximal isokinetic knee extensions at 120°·s⁻¹ on the same day: 50 CON followed by a work-matched ECC bout (∼5000 J; 28 ± 5 reps) with the contralateral limb. Ultrasound images were captured from the middle and distal sites of the vastus lateralis before and immediately after each exercise bout. From these images, MT and PA were measured. Middle and distal MT (11% and 14%, respectively; p < 0.001) and middle PA (39%, p < 0.001) increased only after CON. In addition, changes in MT were strongly related to the amount of total work performed (r = 0.76) during CON. Our results suggest that when the workload is matched between CON and ECC muscle actions performed at a moderate velocity, CON actions seem to be a more potent stimulus for inducing acute changes in MT and PA.