Serena found herself 3-0 down in a matter of minutes but was hugely impressive thereafter in a 6-3 6-2 victory over Italian, Pennetta.
The five time US Open champion said she “had a lot of fun” and is one of only two top-10 seeded players left in the tournament alongside 10th seed Caroline Woznaicki
“I’ve had a tough year in the majors,” added Williams. “I’ve gone down to some great players outside of the top 10 so you can never underestimate anyone. We’re all fighting really hard and we all deserve to be here.”
She then praised Pennetta, who had never beaten her in five previous meetings, for her resilience. “I felt she was playing really well, I don’t feel I was doing too much wrong (in the first three games).
“I just said to myself that if she keeps it up then she absolutely deserves the win and I just tried to do a little better. I had a lot of fun today, I really enjoyed it and I’m so happy to have won”.
Williams has not lost more than three games in any set yet, in this tournament, and will be a big favourite to beat surprise semi-finalist Ekaterina Makarova.
In other games decided at Flushing Meadows, Kei Nishikori defeated third seed Stan Wawrinka in a five-set thriller to make a Grand Slam last four for the first time.
Nishikori came through his second successive four-hour match to win 3-6 7-5 7-6 (9-7) 7-6 (5-7) 6-4.
The 10th seed had beaten Milos Raonic in the fourth round in five sets in a match that finished at 2.26am local time, which is the joint latest finish in US Open history.
His victory over Wawrinka makes him the first Japanese man in the Open era to reach a Grand Slam semi-final after an epic four hours and 15 minute encounter with the Swiss Australian Open champion.
Russia’s Ekaterina Makarova also made it into her first ever Grand Slam semi-final – beating two-time finalist Victoria Azarenka 6-4 6-2.
Azarenka was not at her best in losing to 17th seed Makarova and received a warning after smashing her racquet.
Andy Murray said he was disappointed that Novak Djokovic proved physically stronger in their US Open quarter-final.
Murray lost to top seed Djokovic 7-6 (7-1) 6-7 (1-7) 6-2 6-4 over three hours and 32 minutes at Flushing Meadows.