Judges gave Lopez a 12-round triumph by lopsided scores of 120-108, 120-108 and 119-109.
Lopez improved to 21-1 and took his fifth consecutive victory since losing a 2021 showdown for multiple world lightweight titles to Australian George Kambosos.
Claggett fell to 38-8 with two drawn after dropping his first world title bout to snap a nine-fight win streak.
Lopez defended for a second time the crown he won by defeating Scotland's Josh Taylor last June by unanimous decision in New York. He also beat countryman Jamaine Ortiz in February by unanimous decision in Las Vegas.
Lopez, 26, says he is looking to an eventual move from 140 pounds to the 147-pound welterweight division.
Claggett, 35, stayed in front of Lopez and traded punches with the larger champion through the early rounds, pressing the attack and smothering Lopez to set the pace.
Lopez answered with body blows and uppercuts, matching the Canadian's output and creating space for harder punches by rounds three and four, which Lopez dominated thanks to rocking uppercuts and quick flurries.
Lopez kept Claggett more at bay by the fifth round but the challenger stayed toe-to-toe and exchanged punches round after round.
Two powerful Lopez right uppercuts stunned Claggett in the eighth round and Lopez bloodied the Canadian's nose in the 11th round, staying in command to the finish.
