Bryant shrugged off "flu-like symptoms" to score 40 of the Lakers' points, though he was disappointed to have turned the ball over 10 times.
The Lakers trailed for most of the game but looked set for another come-from-behind win when Bryant slotted a three-pointer to tie the score at 77-77 with 24 seconds left.
Hill had other ideas, however.
He milked the clock before driving hard to the hoop and his floating lay-up bounced on the rim in the last second before dropping through the net.
"It was a great feeling," Hill said. "It's something you dream about all the time, to hit game winners."
Pacers head coach Frank Vogel said he had faith that Hill's shot would come off.
"He works on the floater more than anybody I've ever met, it's his money shot," Vogel said.
"It's a huge confidence booster. What enabled us to build steam towards the second half of last year, and have a great second half of last year, was early road wins.
"We hadn't gotten any yet this year and we talked about this is our opportunity to get that first quality road win and the guys came through."
Hill led the Pacers in scoring with 19 while David West contributed a double-double with 16 points and 10 rebounds.
Both teams struggled with accuracy from the floor but the Lakers were particularly guilty of poor shooting, making 32 percent of field goals and missing 20 free throws.
"It's hard to win a game when you miss 20 foul shots, are six from 28 from the three, and shooting 32 percent," Lakers coach Mike D'Antoni said.
"They had a chance to win, which defies the logic. Defense is good, they played hard and it's just offensively. That was not nice. That was tough."
Bryant cut a dejected figure in the locker room after the loss, clearly feeling the effects of his illness.
Despite grabbing 10 rebounds and scoring a game-high 40 points, he was unhappy with his contribution to the team.
"I was just tired," he said. "You just feel drained.
"But it boggles my mind that I had 10 turnovers. My responsibility is to pick everybody up. It doesn't matter if we miss 20 free throws, we still could have won the game.
"The fact is we had 10 possessions where we couldn't get looks at the basket because I turned it over."
The result left both teams at 7-8 for the season.
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