Russian 17-year-old Mirra Andreeva, coming off back-to-back WTA 1000 wins in Dubai and Indian Wells, also exited in the third round, her 13-match winning streak ending with a three-set loss to American Amanda Anisimova.
The 6-4, 6-2 win for Eala over fifth-seeded American Keys prompted her to hug her team and celebrate passionately after she became the first woman from the Philippines to beat a top-10 opponent since the ranking system came into being in 1975.
Eala, the 2022 US Open girls' singles champion who has been based at the Rafael Nadal academy in Mallorca since she was 13, will now take on Spain's Paula Badosa for a spot in the quarterfinals.
"Growing up it was tough," she said. "You didn't have anyone from where you're from to pave the way. Of course, you had many people to look up to around the world, but I think - I hope this takes Filipino tennis to the next step," Eala said in her on-court interview.
Keys, who was badly beaten by Aryna Sabalenka in the Indian Wells semi-finals, conceded she was well short of her best form.
"My serve was not really there today and I just kind of felt a little flat - and when you are playing someone who makes a ton of balls back and absorbs really well, that's not really the keys to success," said the American.
Andreeva, the 11th seed, hoped to continue her rise up the rankings with a strong showing in Miami but appeared to be hampered by injury as she lost to 17th-seeded Miami resident Anisimova.
Andreeva received lengthy medical attention in her abdominal area when 2-1 down in the first set, in which she lost 7-6 (7/5).
She bounced back, dominating the second set 6-2 but Anisimova won the third set of the two-hour and 49-minute battle 6-3.
Anisimova will face Emma Raducanu in the fourth round after the British player advanced when her American opponent McCartney Kessler retired injured in the second set of their encounter.