Hewitt lost his second-round clash with 11th-seeded Frenchman Gilles Simon 6-3 6-3, leaving Bernard Tomic as the lone Australian left in the event.
Tomic takes on US Open champion Andy Murray on Saturday (Sunday AEDT) for a place in the third round.
Azarenka complained of ankle pain after a 6-3 6-1 fourth-round victory over Urszula Radwanska in the Indian Wells quarter-finals last week before withdrawing.
"The last two days I tried to practice, which did not get better so it just gives me a very obvious indication that it's not possible for me to play," Azarenka said.
"It was really obvious what the decision was a couple days ago already. I just wanted to give my 100 per cent possibility to play and today was my last test."
Azarenka, who like all Miami seeds received a first-round bye, is unbeaten on court this year, a 17-0 run that includes the Australian Open and a title in Doha.
But she has twice surrendered matches by walkover, the first in January at a Brisbane semi-final against Serena Williams with an infected right toe that resulted from a pedicure.
The world No.3 said she has no idea when she might return, noting her next scheduled event is in early April at Monterrey, Mexico.
Azarenka was replaced in the Miami draw by 19-year-old US lucky loser Lauren Davis, who saved three match points in the deciding tiebreaker to defeat compatriot Madison Keys 6-1 5-7 7-6 (9-7).
Davis, ranked 81st, never expected to even have the chance to play after watching Azarenka warm up in the morning. Now she awaits either Britain's Laura Robson and France's Alize Cornet to decide a spot in the last 16.
In the men's event, Spanish third seed David Ferrer joined Simon in the last 32 with a walkover when Russian opponent Dmitry Turnsunov withdrew with a stomach bug.
He next faces Italian 32nd seed Fabio Fognini, who beat France's Michael Llodra 6-3 6-1.
Fifth-seeded Juan Martin del Potro of Argentina crashed out, falling 7-6 (7-5) 6-1 to 89th-ranked German Tobias Kamke in a second-round match disrupted by rain.