Sampras ended more than two years of futility by winning his first championship since setting the record for most Grand Slam triumphs at Wimbledon in 2000.
"This one might take the cake," Sampras said. "I never thought anything would surpass what happened at Wibmledon a couple of years ago, but the way I've been going this year, to kind of come through this and play the way I did today, it was awesome.
"This might be my biggest achievement so far, to come through a very, very tough time and to win the Open. That's pretty sweet."
For the first two sets, it appeared as if Sampras reached into his racket bag and pulled out his dominant power game from the late 1990s. The demoralizing serve, the crisp volleys and the punishing forehand were all in evidence as he had his way.
But the former No. 1 showed his true mettle as he tired in the last two sets. After dropping the third set, he fought off four break points in the fourth before breaking Agassi in the ninth game. His deep forehand return elicited a forehand into the net.
"I had a couple of break points (that game)," Sampras said. "He had a couple of good serves to my backhand. I chipped it short. He's not gonna miss those shots. The one that I did convert, I hit a good return deep and it kind of caught him off guard."
Serving for the match, Sampras hit a pair of service winners before nailing a second-serve ace at 119 miles per hour, his 33rd of the day, to bring about three championship points.
Agassi saved one with a crosscourt forehand pass, but Sampras hit a backhand volley to conclude the oldest men's final in the Open Era in two hours, 54 minutes.
With his fifth U.S. Open title in hand, the 31-year-old Sampras threw his arms in the air, embraced his fellow American at the net and strode into the stands to kiss and hug his pregnant wife, actress Bridgette Wilson-Sampras.
"(That) was spur of the moment," Sampras said. "It was to share it with my sister and my wife. You know, those people really are the reason I'm here. I had that support. Because there were moments where I was struggling to continue to play and my wife really supported me and kept me positive and kept me upbeat.
"That support was huge for me at this stage of my career."
Sampras put aside the question of retirement.
"I'm going to have to weigh it up in the next couple months to see where I'm at. I still want to play. I love to play. But to beat a rival like Andre in a major tournament, it might be nice to stop. I still want to compete. I still love to play. I'll see where I'm at in a couple of months, where my heart's at and my mind."
Holding his lowest seeding for a Grand Slam at No. 17, Sampras had not won a title in more than two years. He had gone 33 events without a victory.
Even so, Sampras reached the finals here in 2000 and 2001 only to be routed by lost to a pair of 20-year-olds in Marat Safin and Lleyton Hewitt.
After dominating men's tennis for most of the last decade, Sampras entered the U.S. Open with only a 20-17 match record this year. He had lost in the first round at the French Open, the only major he has yet to win, - and in the second round at Wimbledon, where he has won seven times.
"So much of what I was going through this year was mental," he said. "It wasn't forehands and backhands and serves. It was kind of my head space. I wasn't real positive out there, kind of got down on myself extremely quick out there. All I could do after Wimbledon was start working again, get back to the drawing board."
As the title drought went on, Sampras heard the talk that he was no longer intimidating, that he has lost a step and was not motivated to win again.
After he struggled through a five-set match in the third round with Britain's Greg Rusedski, his opponent said the American great would not win another match in the event.
But the next day, Sampras showed no ill effects from the five-setter as he raised his level of play to defeat third seed Tommy Haas in four sets. He made it look even easier with a straight-sets rout of rising American Andy Roddick in the quarterfinals and another three-setter over Sjeng Schalken. Heading into the final, he had won 104 of his 108 service games.
That deadly delivery was on view Sunday when Sampras blasted two 120 mph aces in the first game. He swept through his second service game with four service winners, including an ace at 129 mph.
Agassi, 32, was matching him game for game, reminiscent of their brilliant quarterfinal clash of a year ago won by Sampras in which neither player lost his serve.
Sampras broke in the eighth game when Agassi hit a crosscourt backhand passing shot wide. He showed his foe a window in the next game when he hit a forehand volley long. But Sampras popped a second-serve ace down the "T" and Agassi missed a backhand pass wide. After he clinched the set with a backhand volley down the line, Sampras pumped his fist and shouted, "Yeah!"
Sampras jumped on Agassi to start the second set, taking a 2-0 advantage. He notched a second break in the seventh game, but Agassi immediately answered. The Las Vegas native got a mis-hit return winner to set up break point before hitting a desperation running forehand lob that Sampras tipped out.
After closing within 4-5 on the next game, Agassi could not break Sampras, who closed out the set with a love game that featured his 15th and 16th aces.
However, Sampras visibly sagged in the third set. His first service percentage went down to 55 as he double-faulted six times. Allowed just that small margin, Agassi put more returns in play.
"I was feeling it a little bit in the third," Sampras said. "I played a lot of matches. He started picking it up, especially on his return of serve. He made me work real hard."
With most of the capacity crowd rooting him on, Agassi broke on the 16th point of the 12th game, putting another return at the feet of Sampras, who volleyed into the net.
"I felt like I still had a little ways to go to secure the momentum," Agassi said. "I felt like now I had a chance to do it. Serving first was important. I had a couple of break points in the third set and I didn't convert those. That turned out to get me."
In the fourth set, Sampras stopped Agassi from taking a 3-1 lead by winning a 20-point game, the longest of the match. After repelling two break points, he hit an inside-out forehand volley to level the set at 2-2.
"It was a massive game," Sampras said. "The momentum definitely switched there in the third. The crowd was getting into it. He had a couple of break points there. I managed to squeak it out. It was a huge turning point just to kind of hold on to serve there."