The 22-year-old had just completed his 43rd lap of the 90-minute session when his car twitched at Turn 1, the back end stepping out and sending him into the outside wall.
In the impact with the SAFER barrier, firstly with the rear-right corner before the right-front corner connected, the car’s nose elevated and the air stream flipped it over.
Herta's car landed on its nose before skating down the short chute towards Turn 2 on its roll hoop and top frame of the aeroscreen.
He remained conscious throughout the incident, reassuring the team he was okay while still sliding upside down, and conversing with his strategist father Bryan as the car came to rest.
Herta has now been checked and released from the infield medical centre. He also passed his first concussion test, but has not yet been cleared to drive again until the car's accelerometer reading is downloaded from the wreckage.
He is due to start 25th for the 106th Indy 500, after a difficult qualifying for the Andretti quintet.
Rookie Romain Grosjean was the best-placed Andretti driver in qualifying with ninth spot, while 2016 Indy winner Alexander Rossi will start 20th. Marco Andretti and Devlin DeFrancesco will line up in 23rd and 24th positions.
Herta's backup car is currently being built up and, as there is no longer a rule that obliges a driver to start from the back of the grid in the event of a chassis change, he can start from the position he qualified.
Herta's crash was the second of the session after Dale Coyne Racing with HMD rookie David Malukas had hit the wall following a clash with Santino Ferrucci’s Dreyer & Reinbold Racing entry.
Malukas, who qualified 13th for his first 500, had moved to Ferrucci's inside into Turn 1 when they made contact, the endplate on Ferrucci’s front-left wing making contact with Malukas’s right-rear tyre.
The Firestone instantly deflated, and Malukas's car looped into a spin, striking the outside wall on the exit of Turn 1 and then sliding along the wall.
Malukas was able to step out unaided, while Ferrucci accepted the blame for slightly misjudging when he could tuck back in behind the rookie.
Malukas's incident was only the second crash during Indy 500 practice, the other being Foyt driver Dalton Kellett’s shunt on Monday.
Tony Kanaan ultimately topped the session ahead of Chip Ganassi Racing team-mate Marcus Ericsson.
Takuma Sato of Dale Coyne Racing with RWR was third ahead of poleman Scott Dixon (Ganassi).
Kanaan, the 2013 Indy winner, and Ericsson were the only two drivers able to lap above 227mph in conditions 16 degrees F cooler than what is forecast for Sunday.
Karam, despite missing the last 20 minutes of the session as punishment for his contact with Malukas, was fifth-fastest.
