The American was drawn in the same quarter as world number five Victoria Azarenka, who faces Karin Knapp in her opening match.
Second seed Agnieszka Radwanska takes on Bojana Jovanovski in her opener, while third seed Angelique Kerber faces Kiki Bertens of the Netherlands.
Top seeds first round draws at French Open 2016
Image credit: Eurosport
Britain's number one, Johanna Konta, playing in her first Grand Slam as a seed, faces a tough opener against Julia Goerges of Germany, while Heather Watson takes on American Nicole Gibbs.
Laura Robson, who has won only one main draw match on the WTA Tour in 2016 and is playing under a protected ranking following her wrist problems, faces 28th seed Andrea Petkovic.
Serena faces a tough path through to the final at Roland Garros as she bids to equal Steffi Graf's record of 22 Grand Slam titles, but it would be very brave to bet against her doing just that and successfully defending her title. For the Brits, Konta faces a tough encounter with Goerges of Germany in her first Slam as a seed, as does Robson against Petkovic, but Watson will be optimistic about beating Gibbs and making a run through the tournament as a good mover on clay.