Next up for the 11th-seeded American is 11th-seeded Johanna Konta, who became the first British woman to reach the Miami Open semifinals. Konta came back from a set down to oust No. 3 seed Simona Halep of Romania, 3-6, 7-6 (7), 6-2 in a match that lasted 2 hours, 30 minutes.
In their first meeting since Wimbledon, Kerber broke serve to open the match against Williams, but the aggressive Williams took command.
"She was playing even better tonight than the last time we played at the semifinals of a Grand Slam, and I don't think you can play any better than that," Williams said. "It's an amazing feeling to be better than the World No. 1."
Kerber staying within one break in the second set and saved four match points, but Williams proved too strong, striking 32 winners to 27 from the German.
"She was really aggressive from the beginning and was hitting the balls really hard," Kerber said. "I think I didn't moved too well today, and made a lot of mistakes, which isn't normal for my game. It wasn't my best game, but she deserved to win because she played really well tonight.
"This wasn't the best start (to being No. 1) I would have wished for, but it's not a drama because I'm still playing good and winning matches. I'm looking forward to playing again."
Konta, after dropping the first set, broke serve for 3-0 second-set lead. Halep evened the set and served for the match at 5-4. She was two points away from victory when Konta denied her.
In the tiebreaker, Halep again saw her lead erased as Konta came back from 5-3 down and won 9-7.
"It was a really tough match, very high level," Halep said. "I was so close to winning, I was two points away in the tiebreak, but she played very strong and deserved to win today."
Konta grabbed the lead in the third set and broke Halep twice to reel off the final five games and complete the comeback and earn a berth in the semifinals.
"Whoever I'm playing, I'll have a battle on my hands, that's for sure," Konta said before the Williams-Kerber match was contested.