Winfrey’s appearance at the DNC had been a closely-guarded secret, kept off the official programme for the night.
She even disguised herself with a hat, sunglasses and face mask for her rehearsal at the venue earlier in the day, according to her friend and CBS host Gayle King.
The audience at the United Center sprang to its feet, cheering loudly when she entered the stage.
Winfrey has previously endorsed Democrats including Barack Obama, but maintained a low profile in 2016 and 2020.
However, she said the country was “fired up” following Kamala Harris’ nomination as she offered a full-throttled endorsement of the US vice president and her running mate, Tim Walz.
A registered independent, Winfrey made an explicit appeal to non-affiliated voters: “I’m calling on all you independents and all you undecideds … Decency and respect are on the ballot in 2024.”
She said: “Let us choose common sense over nonsense, because that’s the best of America. And let us choose the sweet promise of tomorrow over the bitter return to yesterday.”