Pirlo set up Italy's opening goal without even touching the ball, Balotelli headed in the winner early in the second half, and Pirlo then nearly scored himself in stoppage time, slamming a free kick from 30 meters (yards) off the top of the crossbar.
"We take our hats off to their skill," England coach Roy Hodgson said.
It was an evening reminiscent of the 2012 European Championship, when Pirlo and Balotelli combined to lead Italy to the final.
This time, after a few errant passes from Pirlo, the midfield maestro broke open the match by stepping over a cross and fooling the England defenders to let Claudio Marchisio fire in from long-range in the 35th minute.
"Pirlo is a player who can add quality in every area of the pitch," Italy coach Cesare Prandelli said. "Whether it's a tight triangle, going far forward or whatever, he can handle himself in any area."
At 35, Pirlo is a veteran of the Italy squad that won the 2006 title and was wearing the captain's armband for this match in place of injured Gianluigi Buffon. Modest and quiet, his personality couldn't be farther from the brashness that the 23-year-old Balotelli displays.
But brashness can often be a positive trait for a striker.
When England equalized two minutes after Marchisio's goal, Balotelli showed his nose for the goal by attempting a sharply angled lob shot after drawing goalkeeper Joe Hart out of position in first-half added time. England defender Phil Jagielka headed away the danger but that only seemed to increase Balotelli's appetite.
Five minutes into the second half, the AC Milan forward finally found the target, eluding Gary Cahill to head in by the far post following superb work down the right flank and a perfect cross from Antonio Candreva.
"I'm really happy. It's a special feeling," said Balotelli, who proposed to his Belgian girlfriend at the beginning of the week. "I've never played in a World Cup and it's fantastic. I dedicate this victory to my future wife, who is here, to my family, and to my friends."
Balotelli hadn't scored for Italy since October but the enigmatic striker now has 13 goals in 30 appearances for the Azzurri and has silenced any doubts about his first-choice status.
Ciro Immobile had been pushing Balotelli for the center forward spot after leading Serie A with 22 goals and scoring a hat trick in a warmup match last weekend against top-flight Brazilian club Fluminense.
"I think (Balotelli) can score many more," Prandelli said. "I've said it before. He has enormous potential. He needs to convince himself that his movements up front are decisive enough to finish actions. He gave everything he had but I'm convinced he has margins for improvement."
When Immobile replaced Balotelli in the 73rd, the crowd at the Arena Amazonia showered him with a loud applause. And when the final whistle blew, Balotelli put his finger to his lips as if to silence the criticism he routinely faces. Then he winked to a TV camera.
Born in Sicily to Ghanaian immigrants and raised by Italian foster parents, Balotelli is also subjected to racism constantly back home.
Before kickoff Saturday, Balotelli tweeted, "ITALIANS. Whatever squad you support, today there is only the Azzurra squad! Hate, jealousy, contempt, let's put it all aside and ALL be united!"
United with Pirlo, Balotelli and Italy are tough to beat.