The 200-meter freestyle final on Monday night features a loaded field, including Sun Yang of China, Park Tae-hwan of South Korea, American Ryan Lochte, Yannick Agnel of France and world recordholder Paul Biedermann of Germany.
Maybe Phelps knew what he was doing when he dropped the event after qualifying in it at the U.S. trials last month.
And Lochte figures to be the longest shot for gold in the race that gives him another shot at Agnel, who chased him down on the final lap to help France win the 4x100 freestyle relay on Sunday.
It could still be a big night for the Americans, with teenager Missy Franklin a medal threat in the 100 backstroke, Matt Grevers favoured in the men's 100 back, and Rebecca Soni looking to upgrade the silver she won in 2008 to gold this time in the 100 breaststroke.
At the 2004 Athens Games, the 200 free was dubbed the "Race of the Century" due to the presence of Australian Ian Thorpe, Pieter van den Hoogenband of the Netherlands and Phelps. They finished in that order.
Phelps won the race over Park four years ago in Beijing, one of his record eight golds. Now it's up to Lochte to try and keep the title in the U.S.
He failed to do it in a thrilling 4x100 free relay that was the opposite result from Beijing. Four years ago, Jason Lezak ran down Alain Bernard to preserve Phelps' bid to win a record eight gold medals in a single Olympics.
This time, the Americans built a commanding lead over the first three legs. Lochte dove in on the anchor leg with a half-body length lead over the field and was in position to add another gold to his dominating win in the 400 individual medley on Saturday.
But Agnel pulled even with Lochte with 25 metres to go, and the American couldn't hold off the Frenchman.
"I gave everything in the last 50 until he cracked," Agnel said. "In the last 10 metres, I saw that he was really cracking."
Agnel touched in 3 minutes, 9.93 seconds, having gone exactly 1 second faster than Lochte over the last two laps. Lochte and the Americans settled for silver in 3:10.38, while favoured Australia didn't even get a medal. Russia took the bronze in 3:11.41, beating the Aussies by 0.22.
"I was just really excited and I think I overswam the first 50 and it hurt me for the last 50," Lochte said. "But we were able to get a medal, so I guess that's good."
He had little experience in the 100 free and had never competed on this relay at the Olympics. But coming off his big win on opening night, Lochte had the hot hand.
"The 100 free, I don't really swim it. I haven't swum it in a long time," he said. "You would think doing distance events, I wouldn't get tired. But sprinting takes a lot out of you."
Despite predictions that records set during the high-tech suit era would be hard to break, world records are falling at the Aquatics Centre. American Dana Vollmer lowered the mark in the 100 butterfly, then Cameron van der Burgh of South Africa broke another in the 100 breaststroke — denying Japan's Kosuke Kitajima an Olympic threepeat. So far, three world records have been set in two days.
The French also had another reason to cheer.
Camille Muffat won the 400 free over American Allison Schmitt in a virtual match race.
Muffat touched about a half-stroke with an Olympic-record time of 4:01.45, while Schmitt was 0.32 seconds back in second. Defending champion Rebecca Adlington took the bronze in Britain's first swimming medal of the games.
Vollmer rallied over the final lap to win the fly in 55.98 seconds, beating the old mark of 56.06 set by Sweden's Sarah Sjostrom at the 2009 world championships.
"I'm on top of the world right now," said Vollmer, who qualified for Athens as a 16-year-old but missed out on the 2008 games.
Lu Ying earned silver in 56.87. Australia's Alicia Coutts grabbed the bronze in 56.94.
Kitajima was trying to become the first male swimmer to win the same race at three straight Olympics. But, like Phelps the night before in the 400 IM, the Japanese star didn't come close.
Van der Burgh was ahead at the turn and gained over the final lap to touch in 58.46, bettering the mark of 58.58 set by Aussie Brenton Rickard.
Australia's Christian Sprenger took the silver in 58.93, and American Brendan Hansen claimed bronze in 59.49.
"That's as fast as I can go right now, and I'm really pleased with the outcome," Hansen said.
Kitajima faded to fifth at 59.79. The night before, Phelps failed in his bid to win a third straight 400 IM title, finishing fourth while Lochte took gold.