Kerber, a three time grand slam champion, broke serve again in set two to lead 3-1 before serving ahead 4-3.
Guaff reached 15-40 on Kerber's service game before the German struck her second ace of the day to reach 30-40.
Guaff would net a forehand dropshot as well as two additional forehands to trail 3-5.
The American held serve to reach 4-5 before the 33 year old German reached 40-0 in her following service game.
Serving at matchpoint, Kerber struck an ace down the tee, her twentieth winner of the day to close out the match.
Kerber, the only past Wimbledon champion remaining in the ladies' draw, yesterday defeated the 19th seeded Karolina Muchova of the Czech Republic 6-2, 6-3 in the quarterfinals to set up a semifinal meeting with the world number one Ashleigh Barty of Australia.
In September of 2016, Kerber reached her highest ranking ever; number one.
The left-hander is known for her speed, footwork and defensive baseline play.