Kenin made 18 unforced errors in an unconvincing first-set display but broke decisively in the 11th game with her sixth consecutive point as she bagged seven games in a row to open up a 4-0 lead in the second.
World number four Medvedev had a shot at breaking that stranglehold in the US Open final in 2019 against Nadal but went down in five sets.
"I wouldn't be surprised to see Daniil win the tournament," Tsitsipas, ranked sixth in the world, told reporters after his 6-4 6-2 7-5 defeat to Medvedev in the semi-finals.
The relentless Russian will contest his first final at Melbourne Park on Sunday and look to claim his maiden Grand Slam title after beating Tsitsipas 6-4 6-2 7-5 at a floodlit Rod Laver Arena.
Yet Medvedev has now won 20 successive matches and 12 against top-10 opponents, including beating Djokovic on the way to winning the ATP Finals.
Fourth seed Medvedev served like a machine until broken in the third set, which revived the Greek fans in the terraces as Tsitsipas roared to a 5-4 lead.
"I'm happy to manage to keep my nerves because still I didn't make so many bad shots," Medvedev said on court of his anxious third set.
Karatsev became the first man in the open era to reach the semi-finals on his Grand Slam debut and the lowest-ranked player to reach the last four of a major for two decades.
"It gives me more experience, more confidence," Karatsev told reporters after his 6-3 6-4 6-2 defeat. "Now I will be playing all big tournaments without playing the qualifiers.
"The Aussie crowd is so amazing, so it was nice to see," Williams, sporting a "Queen" necklace, told reporters.
"The difference today was errors," Williams said earlier in her news conference. "Honestly, it was opportunities where I could have won. I could have been up 5-Love. I just made so many errors.
The Serbian world number one hit back strongly after losing a tight opening set on a tiebreak but trailed in both the third and fourth sets before turning them around.
Germany's Zverev will rue allowing Djokovic back from 4-1 down in the third set and he was also up 3-0 in the fourth.
World number two Halep is no slouch around the court, and the pair shared 52 rallies of five shots or more during a heavyweight contest on Rod Laver Arena.
"I think 1926, the summer of 1926 I think was the last time I felt that," the 39-year-old smiled.
Sabalenka won three straight games to get back on terms but Williams's experience saw her through as she maintained her unbeaten run since emerging from 14-day quarantine in Australia.
