Williams hadn't competed anywhere since a first-round exit at the US Open on August 29.
That 6-1 6-1 defeat against Greet Minnen was the American's most lopsided loss in 100 career matches at the major tournament she won in 2000 and 2001.
Thursday's defeat ended with Williams getting broken by her Japanese opponent for the seventh time in 12 service games.
Williams, once ranked world No.1 but now outside the top 450, won her most recent grand slam title at Wimbledon in 2008 and has played sparingly in recent years, in part because of injuries.
Her most recent appearance at the prestigious Indian Wells tournament came in 2019.
She can still offer stinging serves and big backhands, but her performance this time was filled with mistakes, including 10 double-faults.
The 80th-ranked Hibino, who came into this match with an 0-3 career record at Indian Wells, will meet No.17 seed Veronika Kudermetova in the second round.
On day two in the desert, with a packed schedule because of postponements caused by the previous night's weather, winners included 2021 US Open champion Emma Raducanu, 2018 Australian Open winner Caroline Wozniacki and the 2022 runner-up at Melbourne Park Danielle Collins.
Next for Collins, who worked hard to beat Erika Andreeva 7-6 (7-3) 7-6 (8-6), is a match-up with world No.1 Iga Swiatek, who edged her in three sets at the Australian Open in January.
Wozniacki battled through a tough first set to beat China's Zhu Lin 7-6 (8-6) 6-1, while Raducanu moved into the second round with a straight-sets victory over Rebeka Masarova.
Raducanu wrapped things up 6-2 6-3 by breaking Masarova, after her opponent had saved three match points, for her fourth win in eight matches in 2024.
"(It was) super-important for me to get through that," Raducanu told broadcaster Sky Sports.
"It's one of the trickiest tournaments conditions-wise to play because it varies so much.
"I dealt with that really well and overcame a really tough opponent who is dangerous in these conditions."
The 2019 and 2021 Australian Open winner Naomi Osaka will next face 14th seed Liudmila Samsonova, after dispatching Italian qualifier Sara Errani 6-3 6-1.