Phelps's unprecedented eight gold medals at the Beijing Games led the United States to a 31-medal haul in 2008, including 12 golds from the 32 events, nine silver and 10 bronze.
The American, who owns 14 Oympic gold medals overall, won't try to match that feat in London, but his seven-event programme gives him plenty of room to make more Games history
Phelps is the two-time defending champion in all four of his individual events -- the 100m and 200m butterfly and 200m and 400m individual medley.
He is aware that no male swimmer has won the same Olympic event at three successive Games.
"I have always wanted to be the first person to do something," Phelps offered obliquely at the US trials, otherwise giving little insight into the personal goals that are driving him at his last Olympics.
However, during Phelps's post-Beijing lull, team-mate Ryan Lochte has emerged as a serious challenger in both medleys.
Their rivalry promises plenty of fireworks, although neither can afford to forget the challenge from the rest of the world.
"It's a pretty big world," US men's head coach Gregg Troy said. "There's a lot of good swimmers out there. I think if we take anything lightly we're making mistakes."
On the women's side, the Americans have a new weapon in Missy Franklin, already a world champion at 17 who is slated for seven events.
The Americans were last beaten in the swimming medals table by the former East Germany at the 1988 Games, and while Australian swimming officials say they expect to claim as many as 15 medals even they don't expect to surpass the USA.
"I think realistically we can be around the total of medals we had in Athens -- 15," Australian head coach Leigh Nugent said, adding: "The gap has closed on us.
"The US are the big challenge. They have dominated swimming for 100 years. There are other players who are making it tougher for us to stay in that number two position," Nugent said.
In 2008, all six of Australia's swimming golds were won by women.
This time around, Australia's team is spearheaded by James "The Missile" Magnusson -- the 100m freestyle world champion and the fastest man ever in a textile suit with a 47.10sec at the Australian trials.
Magnusson is odds-on favorite to give Australia gold in the sport's blue riband event and lead them to victory in the coveted 4x100m free relay.
Leisel Jones is set to become the first Australian swimmer to compete at a fourth Games, while defending 200/400 medley champion Stephanie Rice also returns.
China claimed just one gold medal at the Water Cube four years ago, but they are on an upward curve, picking up four golds at the 2009 world championships and five -- second behind America's 16 -- at the 2011 worlds in Shanghai.
Sun Yang was a star in Shanghai, breaking Aussie Grant Hackett's iconic 1500m freestyle world record.
Another young swimmer, Ye Shiwen, won the women's 200m medley world title, part of a strong Chinese showing in home waters that had head coach Yao Zhengjie saying the nation hoped to make Olympic "breakthroughs" in London.
China's Wu Peng arrives in London with a confidence-building 200m fly victory over Phelps at a Grand Prix meeting in the United States in May under his belt.
Japan brings a strong challenge in backstroker Ryosuke Irie and veteran breaststroker Kosuke Kitajima.
Kitajima won the 100m and 200m breaststroke at the past two Games and like Phelps is seeking to do what no male swimmer has done before -- claim a third straight title in at least one event.
The hosts, meanwhile, hope to give British fans plenty to cheer at the Aquatic Centre.
Olympic champion Rebecca Adlington and world champion Liam Tancock are among the British swimmers aiming for Games glory in front of home fans.
"This GB swimming team is a real mix of tried and tested experienced former Olympians together with an exciting crop of talented youngsters who will sample their first Olympics," British Swimming's national performance director Michael Scott said.
France is another European nation bringing a strong team, although Beijing 100m freestyle champion Alain Bernard failed to qualify for an individual event and travels to London as a possible relay swimmer only.
France's team includes 2004 Olympic champion Laure Manaudou, who goes in the 100m and 200m backstroke.
France's Camille Muffat has demonstrated impressive consistency this season, and turned in a 200m freestyle time of 1:54.66 -- the fastest ever in the textile suits now mandated by FINA.
The ban on polyurethane "supersuits" means that racing, not records, will be at the forefront.
"We're back to a little more true sport," US coach Troy said.