Still showing some rust from her long layoff, Serena hit just one ace and made 37 unforced errors to 32 for Bertens. The triumph at the BNP Paribas Open in Indian Wells, California, comes six months after childbirth.
With 28 previous meetings and a 29th on the way, Venus and Serena have never played anyone else as much - Serena's next-most-played opponents are Victoria Azarenka and Maria Sharapova (21 times each) and Venus' next-most-played opponent is Lindsay Davenport (27 times).
"Obviously, I wish it was anybody else in the draw, literally anybody, but that's okay", Serena said ahead of the match.
Serena and Venus Williams have been battling it out on the WTA Tour for 20 years, and they meet yet again on Monday in the third round at Indian Wells.
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Venus and Serena are scheduled to face each other after 2 p.m. ET on Monday, live on the Tennis Channel and streaming online at WatchESPN. The announcement drew boos from fans, who expressed doubt that she was indeed injured.
Venus did her part to set up the marquee match when she dismantled World No.35 Sorana Cirstea 6-3, 6-4 in just 79 minutes. She said their father, Richard, would probably decide - an insinuation that their matches were rigged. "First of all, 17 years ago seems like forever ago". "You know, we can always stay in the tournament longer if the both of us are in the tournament", Serena said.
Venus is enjoying a resurgence on the Tour after a string of injuries limited her playing time for several seasons.
In the men's section, Spanish veteran Fernando Verdasco used his powerful serve to upset third seed Grigor Dimitrov 7-6 (4) 4-6 6-3 while Roger Federer's tournament debut was hampered by rain.
Over the years, the two sisters have played out some memorable encounters but this one is surely the most unique of the lot. "We have a great little family going on".