The veteran American tennis star lost 6-2 6-3 in the quarter-finals match.
Her opponent Collins came into the matchup having already played nearly 12 hours of tennis in Miami alone, battling through two rounds of qualifying to bring her total of matches to seven.
"The first time I saw Venus in the locker room, I almost cried", Collins said. "I mean, they have no idea".
Specifically, her shoes and shirt were proudly displayed with Leo's name.
"I think maybe the other tournaments I was trying to play more balls in the court and without any aggression" she had admitted before the match.
She will face French Open champion Jelena Ostapenko, who won a tight straight sets victory over Elina Svitolina. It seemed as if the crowd in Miami would be treated to an extremely close second set. Isner nailed 13 aces past the South Korean and missed only one of 32 first serve points.
Williams is known as a strong server but Collins stood firm and matched her.
Collins won an impressive 66 percent of her service points as she was only broken once by Williams.
"It's different if you win a Grand Slam when you weren't even thinking about it, like Sloane did", Murray told ESPN. Along the way she's knocked out the likes of childhood hero and No.8 seed Venus Williams as well as CoCo Vandeweghe and Monica Puig, putting together a fairytale run into the semifinals.
"Overall, what I've done is not bad at all", Azarenka said, summing up her four-week return.
Those circumstances and experiences also motivated Collins to attend - and finish - college, something neither of her parents had done.
Collins topped US Open finalist Madison Keys earlier this month at Indian Wells and made a much bigger statement with this win.
"[Collins] played very well, aggressively", Williams said afterward. She has won Wimbledon five times and will soon turn 38 years old.
Her last win over an American had come against Chirico en route to 2017 Roland Garros title.
All that good work was swiftly undone, however, as an errant forehand relinquished the initiative once more and Azarenka took full advantage, breaking to love in game nine as Stephens netted. Collins needed to survive two qualifying matches before making the main draw at Key Biscayne, and will now meet sixth-seeded Jelena Ostapenko in Thursday's semifinals.
The reigning French Open champion and a surprise American qualifier completed the Miami Open semifinals on Wednesday.