Winfrey took the stage to give out the first award of the night after a fun opening number from host Kenan Thompson.
Taking the stage to present the first award of the night, Winfrey delivered a message about the importance of always getting back up when you get knocked down, regardless of the odds.
"It's the most coveted television accolade on the planet and yet it's impossible to win one -- almost," Winfrey said, holding an Emmy trophy aloft. "There are eight billion people on this planet, but only 25 Emmys to be given out tonight. Your chances of winning? 300 million to 1. So how do you win one? It starts with a dream."
"A dream strong enough to endure the knockdowns and rejections. You can lose a role or a series, but there is one thing you can't lose -- the belief in yourself," she continued. "Without that belief, you'll never succeed. And even with it, you've got, at best, an outside chance."
"Every Emmy nominee tonight has been knocked down, but they got back up. And that's why you're here," Winfrey added. "[They were] voted for, by their peers, as the very best. So let's make some dreams come!"
Ahead of her impassioned speech, the star-studded show kicked things off with a laugh with help from Saturday Night Live stalwart Kenan Thompson. The sketch comedy icon served up some fun as the night's host with a memorable monologue to open the show.
Addressing the audience at the Microsoft Theater in Downtown Los Angeles, Thompson -- who jokingly called himself "The mayor of television" -- strolled through the seated crowd to deliver his endearingly playful monologue.
"Tonight we come together to honor the greatest invention in the history of mankind -- television," Thompson shared. "I mean, if it weren't for TV, what would we do in our free time? Read books? No one in this room has read a book in the last 50 years. Watch TikTok? You mean tiny vertical TV? Or have sex? Gross! TV is all we have."
Thompson then kicked things over to the musical portion, which featured dance-filled modern club remixes of famous classic TV theme songs, including Friends, The Brady Bunch, and a wild Game of Thrones remix.
All the while, Thompson tried his best to dance along with the professional backup dancers and, well, the whole joke seemed to be how unprepared he was for a choreographed routine. It was the kind of weird, lighthearted routine that set the tone for an unpredictable night of fun and excitement.
Thompson -- who won an Emmy in 2018 -- said in a press release in August that he was excited to be a part of the special occasion.
"Being a part of this incredible evening where we honor the best of the television community is ridiculously exciting, and to do it on NBC – my longtime network family – makes it even more special," Thompson shared. "Like all TV fans, I can’t wait to see the stars from my favorite shows."