Williams is in second round action against Victoria Azarenka, which is a repeat of the 2016 final.
On that occasion Azarenka beat Williams 6-4 6-4 and she will be hoping for a similar result again.
Williams has played a competitive tennis match since losing at the Australian Open and could be rusty going into the match.
Meanwhile, Djokovic is teaming up with Fabio Fognini in doubles against Jeremy Chardy and Milos Raonic.
Nick Kyrgios, who in Acapulco last weekend, returns to action in the doubles as well today.
The Aussie plays alongside Taylor Fritz against Steve Johnson and Dominic Thiem.
Other notable matches on Friday include Great Britain’s Johanna Konta against Su-Wei Hsieh.
Daniel Evans faces Stan Wawrinka, Simona Halep plays Barbora Strycova and Alexander Zverev teams up with his brother Mischa in the doubles.
Indian Wells live stream – How to watch
Coverage of the tennis from Indian Wells is being broadcast on Amazon Prime Video.
This year, Prime Video will broadcast on-site, live studio coverage across tournaments, including at the BNP Paribas Open from Indian Wells, the Fever Tree Championships from The Queens Club, the US Open, and the Nitto ATP Finals from The O2.
On-site field reporters will bring customers the latest action, analysis and commentary right from the court side at many tournaments.
In addition to 37 ATP Tour events and the US Open available exclusively on Prime Video with a Prime membership, Prime members in the UK who subscribe to Eurosport Player through Prime Video Channels for an additional £6.99 per month (following a 7-day free trial) will also benefit from full coverage of the French Open, and daily highlights and live coverage from the men’s and women’s finals of Wimbledon in 2019.