By Toby Prince
The world number one was expected to have been given a tough examination by fellow American Keys in their fourth-round contest on Sunday, but needed just 70 minutes to see off the 19th seed on Arthur Ashe Stadium.
Keys had started well before back-to-back double faults handed Serena a vital break in the eighth game of the first set, a mistake the 20-year-old never recovered from.
The 21-time Grand Slam champion broke Keys twice in the second set to record a straightforward 6-3 6-3 triumph and set up a 27th meeting with her sister Venus.
Earlier on Sunday, the older Williams, Venus, ranked 23rd in the latest ATP rankings, dispatched Estonian qualifier Anett Kontaveit 6-2, 6-1 in a match that required only 50 minutes.
Serena leads the head-to-head record against her elder sibling 15-11 and beat her in the last 16 of Wimbledon earlier this year.
However, Serena says Venus has shown recently she has what it takes to end her bid for a calendar Grand Slam.
“She’s playing great,” Serena said. “I have to really be ready for that. At least one of us, a Williams, will be in the semis.
“I served much better today. I’m so proud I was able to serve better. I had to; I knew I wouldn’t have too many chances to break.”