Williams, who was on a brilliant run after knocking out some big names, was taken for a drive from the 20-year old as her skills exhausted the 37-year old American.
Wozniacki blew a 3-0 lead in the first set and was on the run most of the match before losing for the second time this year to Daria Kasatkina.
Serena leads Venus 17-11 all-time and has won eight of their last nine meetings, most recently the Australian Open final last year.
Williams' only competitive appearances since the birth came in December at an exhibition in Abu Dhabi, a Fed Cup doubles match with sister Venus last month and an exhibition in New York on Monday.
In his opening round in the main draw, Yuki will fight it out with fellow qualifier Nicolas Mahut, ranked 101, and if he manages to cross the first hurdle he will be up against world number 12 Lucas Pouille.
Indian Wells, Mar 7: World No. 1 Novak Djokovic and fourth-ranked Caroline Wozniacki will defend their titles at the $11 million Indian Wells ATP and WTA hardcourt event that begins on Wednesday. The record prize
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