The new show, developed by So You Think You Can Dance's Nigel Lythgoe, will see unknown acts being given the chance to open for established musicians.
Lythgoe and his Artist Development Team, which includes Mary J Blige and producer Antonina Armato, search the internet to find amateur stars and then send Olivia Lee to offer them the opportunity to perform as an opening act.
However, they will only have days to prepare and the show will follow them as they attend an intensive "performance boot camp", have mentoring sessions and then face the all-important shows.
Among the acts the participants could be paired with are Nicki Minaj, Rod Stewart, LMFAO, Brad Paisley, Jason Aldean, Jason Mraz and Gym Class Heroes.
E!'s president Suzanne Kolb said the show will feature "truly talented, passionate people", adding: "They weren't seeking fame, but thanks to Nigel, his team and the headliners, fame came knocking on their door.
"With this unexpected break and whirlwind journey comes raw emotion, nerves and intense preparation. The question is whether or not the opening acts can truly seize the moment and use this extraordinary opportunity as a stepping stone to the career they never thought possible."
Meanwhile, Lythgoe claimed that there is "an extraordinary amount of untapped talent out there", saying: "If you don't know the right people or have the right connections, you may never be discovered.
"With Opening Act, we are democratizing a notoriously impossible process, pulling back the curtains on a consistently fascinating industry, and affording aspiring artists the chance of a lifetime.
"Each one has their own distinct story, but they all dream of their one chance to shine. Every week, we'll provide that spotlight... and turn it up to 10,000,000 watts."
Opening Act will premiere July 9 on E!.