The Yankees said he would undergo surgery later in the evening at Chicago'sRush University Medical Center.
Fowler stayed on the ground for several minutes before medics stabilized his knee. He was eventually hoisted onto a cart and driven off the field. Yankees manager Joe Girardi said he was rushed to the hospital because doctors were worried about an infection.
Girardi said Fowler's season is over and the manager thought the recovery time would be at least six months.
Fowler was due to lead off the second inning. It would have been his first major league at-bat.
Girardi put his hands over his face as team trainer Steve Donohue attended to Fowler down the right-field line.
"I was in tears, actually," Girardi said. "Because I know what it takes to get here and how hard he has worked and what is supposed to be a really exciting day for him turns into a really bad day. I'm still in in disbelief. I'm in tears for the kid."
Fowler's teammates on the field and in the dugout all watched with concerned looks on their faces
"I was sick to my stomach," said Aaron Judge, the Yankees' regular right fielder who DHed on Thursday.
Fowler initially tried to regain his footing but collapsed to the ground. He showed little emotion.
"It is one of the worst things I've seen on a baseball field," Yankees left fielder Brett Gardner said.
Girardi blamed what he described as an electrical box that was at the top of the short wall for the severity of the injury.
"I'm not blaming the White Sox, but it is something that needs to be inspected," Girardi said. "It should've been padded or not put there or put lower because if the kid doesn't hit the electrical box, he might still be hurt but my guess is he doesn't rupture his patellar tendon."
Girardi also said MLB needs to figure out a better plan than having the short walls in foul territory in the outfield. He said plexiglass, like in hockey, should be considered.
It was unclear whether the wet surface had anything to do with the injury. Girardi did not bring that up as a factor. The teams were delayed by rain for 2 hours, 50 minutes, moving first pitch to 10 p.m. CT.
Fowler was unavailable for comment.
Fowler, 22, is another of the Yankees' long lists of prospects. A left-handed hitter, he batted .293 with 13 homers and 43 RBIs in 70 Triple-A games. Scouts have compared him to a young Steve Finley.
After a long flight from Syracuse to Chicago on Thursday, Fowler arrived saying he felt "overwhelmed" with excitement and happy to be in the lineup.
Because of the short notice, Fowler's family could not join him in Chicago, but they were scheduled to meet Fowler and the Yankees in Houston on Friday.
Fowler carted off in first MLB game
Making his Yankee debut, Dustin Fowler crashes into the wall trying to make a catch in the first inning, suffering an open rupture of the patellar tendon in his right knee, before recording his first MLB at-bat.