Azarenka, seeded second, and Hantuchova played in the night session on Arthur Ashe court and the Belarusian cruised to a 6-2, 6-3 victory by converting 7- of-11 break point opportunities.
"I felt like I was really good in the important moments," Azarenka said. "In the first set I really, towards the end, raised my level where I wanted to, and that was what was I think the key to this match."
Azarenka has reached the semis in six of the past eight majors. Hantuchova has played in just one Grand Slam semi in her career.
The 31-year-old Pennetta upset 10th-seeded fellow Italian Roberta Vinci 6-4, 6-1 on a sun-drenched day at the USTA Billie Jean King National Tennis Center. Pennetta ousted fourth-seeded compatriot Sara Errani in the second round here last week and has perhaps reestablished herself as Italy's best player.
Following a competitive opening set, Vinci appeared to give very little effort in the second, as the uneventful bout was over in 65 minutes at Ashe Stadium.
"I'm really happy. I cannot believe it," said an elated Pennetta, who has yet to drop a set at this Big Apple fortnight.
Pennetta improved to 5-4 lifetime against Vinci, including 2-0 at Grand Slam events.
The 30-year-old Vinci was playing in her second straight U.S. Open quarterfinal (0-2). She's never played in a major quarter outside of New York.
Vinci and Pennetta were two of five thirtysomethings in the quarterfinals here, equaling the most in the Open Era at any Grand Slam event.
The world No. 83 Pennetta played in her fourth U.S. Open quarterfinal in her last five trips to Flushing. She missed last year's Open because of a right wrist injury.
This will mark Pennetta's first major semi in 41 Grand Slam events. She's never advanced beyond the fourth round at the Australian Open, French Open or Wimbledon.
Pennetta and Azarenka have faced each other just twice, last meeting in Dubai in 2011. Pennetta won that match in three sets, while Azarenka defeated her in 2010.
The other semifinal will pit top-seeded Serena Williams against fifth-seeded Li Na, who was this year's Aussie Open runner-up and is a former French Open champ.
The 16-time Grand Slam titlist Williams is a four-time U.S. Open champion and two-time runner-up. She beat Azarenka in last year's finale in Flushing and captured the French Open back in June.
The 2013 U.S. Open champ will earn $2.6 million. The current world No. 1 Williams would claim an additional $1 million as a result of capturing the U.S. Open Series.