He will be the first swimmer to be the flag-bearer since Gary Hall in 1976, leading the American team in Friday's opening ceremony.
"I'm honored to be chosen, proud to represent the U.S., and humbled by the significance of carrying the flag and all it stands for," said Phelps, who is the most decorated Olympian of all time with 22 medals.
"For Sydney, I just wanted to make the team. For Athens, I wanted to win gold for my country. For Beijing, I wanted to do something nobody else had done. In London, I wanted to make history.
"And now, I want to walk in the opening ceremony, take it all in, represent America in the best possible way and make my family proud. This time around, it's about so much more than medals."
Phelps retired after the London 2012 Olympics, where he took his career haul to 18 gold medals, but came out of retirement two years later.
He was banned for six months after being arrested for drink driving and speeding, missing the 2015 world championships, but subsequently qualified for the 100 and 200 meters butterfly plus the 200m individual medley.
Now 31, he is only the second American swimmer to have qualified for five Olympic Games, and the first male.
Phelps will resume his rivalry with U.S. teammate Ryan Lochte in the 200m medley, while he will have the chance to avenge a rare defeat in the butterfly.
While Phelps beat Chad le Clos in the 100m in London four years ago, the South African claimed a notable success in the 200 as he defeated his childhood hero -- winning by just 0.05 seconds.
"When I turned, I actually looked at him underwater and I actually kind of thought I was him," le Clos told CNN in 2015
. "That sounds absolutely crazy but I saw myself as him coming past someone else."
His father's ecstatic reaction when interviewed on British television
, which included numerous uses of the word "unbelievable" and a tribute to his "down to earth, beautiful boy," also made headlines around the world.
While Phelps has been dealing with his own demons
, le Clos revealed in July that both his parents were suffering from cancer.
"It has not been an easy time but I am training hard for Rio," he said in a statement
. "More than anything else I want them to win their battles. I also hope that they will be in Rio."
While it will likely be hard to put such serious concerns to the back of his mind during competition, le Clos has never been short of self belief.
"I've always believed that I was best," he told CNN in 2015. "Maybe necessarily when I wasn't the best, I know that when I get on that block, I look at whoever I'm racing, I don't care who you are, I believe that I can beat you."