The grueling race encompassing all four strokes is an appropriate way for one or the other to fire the first salvo in this most intriguing of rivalries.
"A very rough race," said Phelps' coach, Bob Bowman, smiling at the possibilities. "It will be a coach's dream, but also a spectator's dream. It will be fantastic."
For Phelps, it's a chance to add to his record total of 14 gold medals and become the first male swimmer to win the same event at three straight Olympics. But Lochte is the defending world champion and defeated Phelps rather easily at the US trials last month.
Lochte is certainly not lacking confidence.
"Right after Beijing, I had a four-year plan for getting here to London," he said. "I thought I could go a lot faster. I knew I could, just because of the training I've done. That's why I knew this was going to be my year."
Lochte started following the same training regimen used by burly athletes who can compete in Strongman competitions - rolling large tires, tossing kegs, dragging chains. He believes it's made him stronger than anyone else in the pool. He believes it's the edge he needs to beat Phelps, and everyone else.
"It's going to pay off," Lochte said. "I just know it."
The Phelps-Lochte showdown won't be the only event on the opening night of swimming.
The home crowd will be cheering on Britain's Hannah Miley in the women's 400 IM, where she'll be competing against American teenager Elizabeth Beisel and California-based Katinka Hosszu, the latest in a long line of Hungarian medley specialists.
The men's 400 freestyle looks like being a tussle between China's Sun Yang, South Korea's Park Tae-hwan and France's Yannick Angel. Ranomi Kromowidjojo leads the Flying Dutch in the women's 4x100 free relay, an event the Netherlands won at the last Olympics and the past two world championships.
The Americans will look to challenge with a relay squad that potentially includes Natalie Coughlin, who won six medals in Beijing but didn't even qualify for an individual event for these games.
The 29-year-old was knocked off at the US trials by an emerging wave of teenage stars, including Missy Franklin, but managed to claim a spot on the team as a possible relay swimmer by finishing sixth in the 100 free.
Without a strong showing in the preliminaries, she might not even get a chance to swim the evening final. But, if the Americans finish on the podium, a morning swim would be good enough to give Coughlin the 12th medal of her career, drawing level with Dara Torres and Jenny Thompson as America's most decorated female Olympian.
But those races are mere warmups to the main event.
Phelps is chasing more history at these games, having already claimed the record for most golds - five more than anyone else - and knocked off Mark Spitz's iconic Olympic standard with eight wins in Beijing.
His next target is Soviet gymnast Larisa Latynina, who is two ahead of Phelps with 18 career medals. It shouldn't be too much of a challenge for him to take down that record, since he's got seven events in London and is confident of winning a medal of some color in every one of them.
Lochte doesn't mind Phelps winning silver or bronze. Those colors don't interest the laid-back Floridian in the least.
"You should be going in with the mindset of winning," Lochte said. "That's what I'm going to be doing each race. I'm going up there to win. I'm not going for silver or bronze, I'm going for gold."
Phelps will certainly have something to say about that. He struggled to stay motivated after Beijing, and some lackluster training showed at last year's world championships, where he was beaten by Lochte in both the 200 free and 200 individual medley.
But Phelps has clearly regained his racing edge, wanting to go out in style at what he insists will be the final meet of his career. He intends to retire as soon as his final Olympic race is over.
"Last workout ever," Phelps tweeted Friday morning, joking that he wouldn't have to do anymore "garbage yardage" and thanking his coach for guiding him throughout his career. "Now let's have some fun this week."
Phelps showed he means business by beating Lochte in both the 200 free and the 200 IM at the US trials. While Lochte took the 400 IM, Phelps only restored that event to his program earlier this year, after vowing to give it up after Beijing. He aims to be faster in London than he was in Omaha.
"It's always a challenge to have things go perfectly," Phelps said. "For the very first night, it is going to be a challenging race. It's going to be an exciting race. Bob and I have changed a few things over the past few weeks, and we'll see what's going to happen in that race. I feel confident. Everything feels good."
Lochte vows he'll also be a lot faster than he was at the trials.
"I knew that wasn't my meet," he said. "That was just a little appetizer, I guess. This is the big show. This is what I've been working for. I wasn't working for trials. I was working for the Olympics."