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.
World number four Coco Gauff, coming off a semi-final run in Dubai, takes on qualifier Kamilla Rakhimova of Uzbekistan, and 16th-seeded Naomi Osaka of Japan faces qualifier Victoria Jimenez Kasintseva of Andorra.
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.