Rune and Zverev crash out of Shanghai Masters on day of upsets
World number five Rune never found his rhythm as he fell 6-0, 6-2 to 22-year-old American Brandon Nakashima, ranked 122nd in the world.
Despite the crowd enthusiastically cheering the Dane on, Nakashima made short work of Rune, defeating him in an hour and nine minutes.
"I had to play my best tennis to pull through," Nakashima said after the match.
"(Rune) is a player who has been at the top of the game for a while so I know against him it's going to be tough every time."
There was also an upset for Alex de Minaur, who fell 6-3, 7-5 to Hungarian Fabian Marozsan, who is ranked 91st to the Australian's 11th.
It was Marozsan's second high-profile knock-out of the year - in May he inflicted a shock defeat on Carlos Alcaraz at the Italian Open.
Hungary claimed another top-20 scalp later in the afternoon, when 31-year-old Marton Fucsovics beat the world number 15, Canadian Felix Auger-Aliassime.
Fucsovics, ranked 57th, ripped off his shirt and roared in jubilation after a tightly fought match that lasted almost three-and-a-half hours and ended 7-6(3), 4-6, 6-3.
Qualifier Yu Hsiou Hsu meanwhile dismissed the world number 18, Lorenzo Musetti, in straight sets.
Zhang makes history
Things went more to plan for a dominant Casper Ruud, who cruised through to the third round by easily dispatching Japan's Yoshihito Nishioka 7-5, 6-0.
And 26-year-old Zhang Zhizhen made history in his hometown, becoming the first Chinese player to progress to the third round of the tournament with a nail-biting win over Argentina's Tomas Martin Etcheverry.
Before a raucous crowd who bellowed encouragement at every opportunity, Zhang determinedly fought back from a first-set loss to eventually prevail 4-6, 6-3, 6-4.
Earlier, Serbia's Dusan Lajovic continued his progress through the tournament after opponent Tallon Griekspoor retired from the match due to illness.
Alcaraz, the top seed in Shanghai in the absence of Novak Djokovic, was mobbed by fans as he made his way to training Friday.
Italy's Jannik Sinner, who beat Alcaraz in Beijing earlier this week before going on to win the China Open, was also looking relaxed and smiling on the practice courts.
Both Alcaraz and Sinner are in action on Saturday, the latter against the United States' Marcos Giron, ranked 80th in the world.
"He's a very, very good player, moving very, very fast, so it's going to be a very difficult match for me, especially as first rounds are never easy," Sinner said Friday.
"I'm very focused and obviously happy to be here, so hopefully, I can start off in a positive way."