Serena, who won her fifth match in a row against Venus, will face Jelena Jankovic who beat Stefanie Voegele 6-4 6-7 6-2 in Sunday's final as she goes for her third Family Circle title.
She needed only 22 minutes to take the first set against the fifth seed, delivering eight winners to zero unforced errors.
Serena, 31, then took the second set over 32-year-old Venus in 54 minutes to prevail for the 14th time in 24 matches against her sister.
"Venus has had a great week, and honestly, if she hadn't had to play so many matches, it would have been a much tougher match," Serena told reporters.
The semi-final came a day after both had played third-round and quarter-final matches on Friday because of weather.
"She'll never admit it, but I don't think she was 100 per cent," Serena said. "But you will never get that out of her. And quite frankly, three matches for her is much tougher than three matches for me. It's definitely not easy - because I'm struggling, and I can't imagine what she must be feeling."
WTA Charleston semi-final results
1-Serena Williams (U.S.) beat 5-Venus Williams (U.S.) 6-1 6-2
9-Jelena Jankovic (Serbia) beat Stefanie Voegele (Switzerland) 6-4 6-7(6) 6-2
WTA Monterrey semi-final results
1-Angelique Kerber (Germany) beat 3-Maria Kirilenko (Russia) 6-4 2-6 6-2
5-Anastasia Pavlyuchenkova (Russia) beat Monica Niculescu (Romania) 3-6 6-2 6-4
- Sports & Recreation
- Jelena Jankovic
- Stefanie Voegele