Italy finished a man down and the Americans ended with only nine men.
Alberto Gilardino put Italy in front with a diving header in the 22nd minute and defender Cristian Zaccardo gave the lead up with an own-goal five minutes later.
Both Pablo Mastroeni and defender Eddie Pope were sent off for the Americans after Daniele De Rossi was red-carded for Italy.
Italy coach Marcello Lippi said the team paid for the energy output in its 2-0 opening win over Ghana five days ago and the corruption scandal that has hung over the team since it began training camp.
"It's human. Our guys worked with an incredible amount of intensity to prepare for this World Cup with all of those things going on and I don't think we recovered from our first game," Lippi said.
"It was a very different approach and we had problems from the start. We missed passes, we couldn't combine plays and that led to nervousness like with De Rossi and other problems."
Italy now has four points to top the group. The Czech Republic and Ghana have three points each and the Americans are last with one.
Italy plays the Czech Republic in its final group game on Thursday and the United States closes against Ghana.
"Our World Cup begins now. From here on, it's win or you're out," Lippi said.
Italy extended its unbeaten streak to 20 games, the second longest streak in Azzurri history. Italy went 30 games without losing from 1935-39, a period that included the country's second World Cup title in 1938.
The United States showed significant improvement from its opening game.
"There's no way you can train a team to play 10 against nine for 40 some odd minutes in a World Cup and our guys did a tremendous job," United States coach Bruce Arena said. "A lot of teams would lose their composure."
Coming off a comfortable win over Ghana, Italy appeared unprepared for the Americans' disciplined play at the start.
Playmaker Francesco Totti picked up a yellow card in the fifth minute for a sliding tackle on Clint Dempsey.
In the 15th, Bobby Convey's free kick was deflected wide off an Azzurri wall. A minute later, Convey had another chance but shot high from 12 meters (yards).
Dempsey's shot was also off the mark in the 18th.
Pope was given a yellow card for taking down Gilardino in the 21st and the Italian gave his team the lead a minute later.
The AC Milan forward slipped past the American defense to connect with Andrea Pirlo's free kick for his eighth goal in 17 appearances for Italy.
Zaccardo's clearing attempt on a cross from Convey in the 27th went in the wrong direction and ended up in Italy's goal to even the match.
In the 28th, De Rossi elbowed Brian McBride in the face while going up for a header, warranting a red card and drawing blood from below the left eye of the American forward.
At 22, De Rossi is the youngest player on Italy's team. He was also given a yellow card for an aggressive foul early in Italy's win over Ghana.
De Rossi's exit prompted Lippi to replace Totti with physical midfielder Gennaro Gattuso in the 35th.
Terms were leveled when Mastroeni, a defender, was expelled for taking out Andrea Pirlo's legs from behind in the 45th.
Uruguayan referee Jorge Larrionda warned U.S. defender Oguchi Onyewu for slapping Luca Toni before halftime.
Two minutes into the second half, Pope picked up his second yellow card for a foul from behind on Gilardino, reducing the Americans to nine men.
Pirlo's ensuing free kick went wide and U.S. defender Carlos Bocanegra almost scored an own-goal off another free kick by Pirlo in the 52nd, heading the ball off his own crossbar.
Lippi inserted Alessandro Del Piero for Zaccardo in the 54th and Vincenzo Iaquinta replaced Toni in the 61st as Italy went for the win.
DaMarcus Beasley came on for the United States in the 62nd and had a goal waved off for offside three minutes later.
"We gave everything at the end to get a point," United States captain Claudio Reyna said. "We have a super team spirit."
Italy picked up another yellow in the 70th when Gianluca Zambrotta fouled Steve Cherundolo.
Del Piero produced two shots on goal in the 73rd and 79th, but both were rebuffed by goalkeeper Kasey Keller.