The 27-year-old two-time world champion posted a 93.3 in his first ride and watched as the other eight riders failed to catch him.
Capping a brilliant performance by the entire Aussie women’s team, McKeon followed her victory in the 50-freestyle earlier in the session to take the butterfly leg on the relay.
The top four were close nearly the entire race, often separated by less than a second at the turns.
Dressel has one more shot at a gold in the 4×100 medley relay, an event the United States has never lost at the Olympics.
If Dressel claims a fifth victory, he would join Americans Michael Phelps, Mark Spitz and Matt Biondi, as well as East Germany’s Kristin Otto, as the only swimmers to win as many as five golds at a single Olympics.
Claes and Sponcil entered the games as the hottest team in the world, winning the last two events of the pandemic-extended qualifying period to grab the second U.S.