The 22-year-old Spaniard made history in Melbourne last month with his victory at the Australian Open, becoming the youngest man ever to complete a career Grand Slam.
He followed up with the Qatar Open to arrive in California on the back of 12 straight wins.
Great Britain's Jack Draper launched his title defense with a 3-6, 6-3, 6-2 victory over Spain's Roberto Bautista Agut.
Draper halted Alcaraz's bid for a rare Indian Wells three-peat in the semifinals last year before beating Holger Rune in the final.
That victory launched his rise to fourth in the world, but he returned to California in rebuilding mode again after an arm injury forced him to cut short his 2025 season.
"To come out and play the level I'm playing after the injury I had, I am really proud of that," said Draper, who made his return to the tour in Dubai last week having not played since his second-round withdrawal at the US Open.
"It was difficult," the oft-injured Draper, now ranked 14th, said of his latest comeback bid.
"Even though from the moment I got here last week, I have felt the love and special feelings being back here, but at the same time I haven't played in a long time and have had a difficult injury, so mixed emotions.”
"But I am really glad with the way I came through in the second and third sets against a formidable opponent in Roberto."