Returning to the pool for the morning heats after they teamed up to win gold for the United States in the 4x200 freestyle relay on Tuesday night, the pair were untroubled making the top 16 for the evening semi-finals.
Phelps, who won the 200 medley at Athens in 2004 and Beijing four years later and is bidding to become the first man to win the same individual event at three Olympics, finished second in his heat and fourth overall despite being fatigued.
"Didn't really get much sleep last night, didn't warm down at all, so this morning didn't feel too comfortable," he said.
Lochte won his heat and was second overall but was conserving his energy because he swam the 200 backstroke heats just before the medley.
"This morning's races were easy. All I had to do was get a lane for tonight and that's what I did," Lochte said.
The fastest overall time was set by Laszlo Cseh of Hungary, who left nothing to chance after missing out on a place on the final for the 400 medley.
South Africa's Chad le Clos was 11th overall. Le Clos upset Phelps in the 200 butterfly final on Tuesday and was so shocked by his victory that he slept with his gold medal.
Shortly before the 200m IM, Lochte safely navigated his way into the semi-finals of the men's 200 metres backstroke.
Lochte won his morning heat in a time of one minute 56.36 seconds to qualify second fastest overall behind his American team mate Tyler Clary.
Lochte is the Olympic champion in the event and the clear favourite to win the gold but faces an extra challenge because he is swimming the 200 individual medley against Michael Phelps on the same days.
China's Zhang Fenglin was third fastest overall in the backstroke heats, just ahead of Japan's Ryosuke Irie.
Rebecca Soni made the perfect start to the defence of her women's 200 metres breaststroke title when she set the fastest time in the heats.
The American showed no lingering effects of her narrow loss in the 100 breaststroke final two days ago as she glided her way through the pool to win her morning heat in a time of two minutes, 21.40 seconds.
She was more than a second, a big margin in elite swimming, ahead of her nearest rival, Denmark's Rikke Pedersen.
The top 16 advanced to Wednesday night's semi-finals from which the fastest eight will go through to Thursday night's final.
China's Tang Yi set the pace in the preliminary rounds of the women's 100 metres freestyle.
Tang swam a personal best time of 53.28 seconds to win her morning heat and finish first overall in the race to discover the fastest woman in water.
Australia's Melanie Schlanger, who won a relay gold medal on Saturday, won her heat in 53.50 to be second overall, just ahead of Denmark's Jeanette Ottesen Gray and Aliaksandra Herasimenia of Belarus, who dead-heated in last year's World Championships final.
With the top 16 advancing to the evening semi-finals, there were no major casualties in the preliminaries although Australia's Cate Campbell and Sweden's Therese Alshammar both pulled out of their heats because of illness.
Campbell, who teamed up with Schlanger to win gold in the 4x100 freestyle final, withdrew because she was suffering a bout of gastro while Alshammar had a pinched nerve in her back.
Colorado teenager Missy Franklin qualified 10th, just two places behind her American team mate Jessica Hardy.
"I think I did a good job. I had a controlled easy swim, faster than I was expecting," Hardy said.
Germany's defending Olympic champion Britta Steffen scraped into the semi-finals as the 14th qualifier. The final will be held at London's Aquatic Centre on Thursday.
"I am happy to have the chance to swim again this afternoon," Steffen said. "Perhaps I can get in a bit more rhythm then. I would love to get into the final, but I realise there are youngsters up and coming."