Vondrousova, who beat 2018 runner-up Daria Kasatkina and former French Open victor Jelena Ostapenko on the way to the fourth round, will go for another big win when she faces sixth-seeded Elina Svitolina, who battled to a 7-6 (10/8), 5-7, 6-4 victory over Australian Ashleigh Barty.
While it is being assumed it was just one of the bad days for Nole, there are debates that Nole was under pressure due to off-field controversy.
Djokovic, 31, said he had already put the defeat behind him and has turned his attention to next week's Miami Open.
In another upset earlier, Pole Hubert Hurkacz fired 10 aces en route to a 4-6 6-4 6-3 win over world number seven Kei Nishikori of Japan to reach the fourth round.
Kohlschreiber's win over Djokovic was also his first career win over a top-ranked player, and he will look to continue his success against France's Gael Monfils in the fourth round.
"It's always a bit tricky whenever you change someone in the team, but I feel like for a first tournament we did really well", Osaka said.
"I'm going to try to go all the way here in doubles".
"I really wasn't focusing so much on her".
"Things to work on, without a doubt", Djokovic said. "I'm not at my highest level, I know that. but hopefully I'll be able to peak in Miami".
But in a match that resumed after rain stopped play following completion of just one game on Monday night, Kohlschreiber looked crisp and confident, breaking the Serbian star for a 4-3 lead in the first and pocketing the set with a service victor on his second set point.
"It's a very special win today", Kohlschreiber said after the match.
"I lose to Kholi and get absolutely shredded "same old kyrgios" how about the guy is just good?"
"Today, with Novak being number one, top-seeded here, it's a very incredible win for me". I'm hitting the ball well. Her triumph in Australia made her No. 1 for the first time, but her time at the top has been rocky.
Andreescu improved her match record for 2019 to 25-3, including qualifying, as she became the youngest player to make the last eight at Indian Wells since a 17-year-old Anastasia Pavlyuchenkova reached the semis in 2009.
Second seed Simona Halep joined the top seeds crashing out after losing 6-2, 3-6, 6-2 to unseeded Marketa Vondrousova of the Czech Republic in one hour and 40 minutes. The 20th-seeded Muguruza upset seventh-seeded Kiki Bertens of the Netherlands, 5-7, 6-1, 6-4, on Tuesday.