Zverev didn't face a break point on a windy Stadium Court, breaking Berrettini's serve once in each set to polish off the victory in just one hour and 11 minutes.
It was an encouraging start for the German, who fell in his opening match last year in the California desert, where he has never made it past the quarter-finals.
"I am very happy with the performance," Zverev said. "He is somebody that is extremely aggressive, massive forehand, massive serve.
"When you back off a little bit, it is very difficult against him, but today I thought I was the one pushing, I was the one being aggressive."
Zverev hopes it's a harbinger of things to come.
"I have struggled in Indian Wells before, but I feel different this year," he said. "Hopefully, it is going to be a different result, and it was a good start."
WTA world number one Aryna Sabalenka and men's No. 2 Jannik Sinner headline the day's play as seeded players swing into action after enjoying first-round byes.
Sabalenka swats Sakatsume aside
Sabalenka, playing her first tournament since a runner-up finish to Elena Rybakina at the Australian Open, took on Japanese qualifier Himeno Sakatsume not long after Zverev's victory, winning 6-4, 6-2 in a little over an hour.
"I'm really happy with the way I was serving, with the way I was putting her on the back foot," said Sabalenka, who has twice reached the Indian Wells final but lost to Rybakina in 2023 and to Mirra Andreeva last year.
Gauff and Shelton hold down homefront
Women's fourth seed Coco Gauff rallied from two breaks down in the second set for a 6-3, 7-6 (7/5) victory over qualifier Kamilla Rakhimova.
Rakhimova, ranked 88th, served for the second set three times, wasting one set point. She led Gauff 5-4 in the tiebreaker before the American reeled off the last three points.
"I felt like if I could get into the tiebreaker, I feel like I have a pretty good tiebreak record," Gauff said. "I knew the odds were in my favor when the tiebreaker started."
Ailing eighth seed Ben Shelton clawed out a 6-7 (3/7), 7-6 (7/4), 6-3 victory over Reilly Opelka in an all-American clash.
Shelton trailed 4-5 in the second-set tiebreaker, but Opelka dropped two points on his own serve, and Shelton held on to level and capture the third set with one more moment of drama when he took a hard fall in the final game.
Mboko and Raducanu advance
In other early matches, Canadian teenager Victoria Mboko, playing her first since cracking the top 10, beat Australian Kimberly Birrell 6-4, 7-6(5).
"It's my first time playing here, so a lot of emotions," said Mboko, whose rise to 10th in the world was cemented with a runner-up finish in the 1000-level event in Doha last month.
"I feel like I've learned a lot in the past year, and I'm still learning. It's just upwards."
Britain's Emma Raducanu, seeded 25th, was quick out of the blocks with a 6-1, 6-3 victory over qualifier Anastasia Zakarova.
Raducanu, ousted in the second round of the Australian Open, arrived in California buoyed by a runner-up finish last month in Romania, where she reached her first final since her upset triumph at the 2021 US Open.
Italy's Sinner, a two-time semi-finalist at Indian Wells, launches his bid for a first title against Czech qualifier Dalibor Svrcina.
Sinner missed Indian Wells last year, serving a suspension for a positive test for the banned anabolic steroid clostebol. He returned from that ban to win Wimbledon and the ATP Finals, but fell to Novak Djokovic in the Australian Open semi-finals and lost to Jakob Mensik in the quarters at Doha last month.
Sinner's fellow Italian Lorenzo Musetti, seeded fifth, faces a tough opener against Hungarian veteran Marton Fucsovics.
Musetti is playing his first tournament since he retired with a right leg injury while leading 24-time Grand Slam champion Novak Djokovic by two sets in the Australian Open quarter-finals.
Follow the men's side at Indian Wells here, and the women's here.