The 64-year-old American, who left a Havana yacht club early Saturday, arrived on a Key West beach yesterday to realise her lifetime quest after four previous attempts failed amid stormy weather and jellyfish attacks.
"I've got three messages," a visibly exhausted but clearly ecstatic Nyad told cheering crowds as she set foot on dry land.
"One is, we should never, ever give up. Two is, you never are too old to chase your dreams."
Initially, the veteran swimmer had hoped to complete the treacherous 160-kilometre trek in 80 hours. But in the end, she did it in 52 hours, 54 minutes and 18.6 seconds, according to her Facebook page.
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"Diana Nyad, 64, has successfully and powerfully realised her #XtremeDream," the posting said.
"Her eyes burned with intensity, her body refusing to quit."
Nyad's pursuit was followed closely by people around the globe, who took to social media to first encourage and then congratulate her.
Live television footage showed crowds swarming the beach and even wading toward Nyad as she approached the shore.
But challenges loomed large during the historic crossing -- especially on the homestretch.
Doctors -- monitoring Nyad from support boats shadowing her -- reported yesterday that her tongue and lips were so swollen that her speech had become slurred.
She also experienced extreme cold overnight, they said.
As Nyad approached Key West, large jellyfish appeared in her path. To keep her from suffering a debilitating sting, divers swam ahead of Nyad looking for more.