Errani and Vavassori claimed their second mixed doubles Grand Slam crown, with the first coming at the US Open last year, where they also defeated Townsend and her longtime former partner, Donald Young.
The title was a seventh overall in Grand Slam doubles for Errani, who also has five women's doubles Grand Slam victories.
"Congratulations to Evan and Taylor, it was so tough to play against you. We had to study a lot," said Errani, who also plays in the women's doubles semi-finals alongside Jasmine Paolini on Friday.
"Thanks to Andrea, to my best friend, it's so much fun to play with you. You're an amazing person and it's so special to be here with you."
The Italian duo were tested early in the first set but saved two breakpoints to secure a tight hold at 1-1, before grabbing the decisive break and taking a 4-3 lead when Townsend sent a forehand wide.
Errani and Vavassori dialled up the intensity to overwhelm their opponents, twice breaking serve in the second set before Townsend netted a volley to give the third seeds a dominant win.
"It's unbelievable to be in another Grand Slam final together," said Vavassori, whose win helped make up for the disappointment of losing the French Open men's doubles final last year.
"We had an amazing run, the US Open was a dream come true and we love to play together."
The American pairing looked disjointed throughout the match and racked up 25 unforced errors, almost three times as many as Errani and Vavassori's nine.
"Thank you guys for cheering us on and taking us through this week. We're running it back at Wimbledon," said Townsend, who teamed up with King ahead of the French Open.
Townsend's previous partner Young quit the sport after their US Open defeat last year to switch to playing pickleball.