Keys was joined by Boyz II Men on Sunday to sing an a capella version of "It's So Hard to Say Goodbye to Yesterday" at the Staples Center — Bryant's stomping ground — as the audience watched in awe.
"Here we are together on music's biggest night celebrating the artists that do it best, but to be honest with you we are all feeling crazy sadness right now," Keys said as she entered the stage, adding that "Los Angeles, America and the world-wide world lost a hero."
She said the audience was "heartbroken in the house that Kobe Bryant built."
"Right now Kobe and his daughter Gianna ... are in our spirits, they're in our hearts, they're in prayers, they're in this building," she added. "Take a moment and hold them inside of you and share our strength and our support with their families."
Before the show officially honored Bryant, Lizzo performed the songs "Truth Hurts" and "Cuz I Love You," saying at the top of the show: "Tonight is for Kobe."
Lizzo was among the mix of newcomers and well-known acts who reached their goals of winning their first-ever Grammy Awards on Sunday, which also included Tanya Tucker, J. Cole, Billie Eilish, Lil Nas X, Billy Ray Cyrus and late rapper Nipsey Hussle.
Michelle Obama, Sara Bareilles, Rosalía and 21 Savage also became official Grammy winners when the show handed out trophies during its pre-telecast ceremony.
Gary Clark Jr. and Eilish's brother, Finneas, walked away as the most awarded stars, so far, taking home three awards each.
Finneas — who co-wrote, produced and engineered his sister's debut album, "When We All Fall sleep, Where Do We Go?" — won best engineered album (non-classical), best pop vocal album (shared with his sister) and non-classical producer of the year.
"My heart is beating so fast right now," Finneas said. "This award belongs to my sister Billie for her trust and vision."
A number of acts won two awards in the pre-telecast, including Lizzo, Lil Nas X and Cyrus, Anderson .Paak, Lady Gaga, Tucker, Kirk Franklin and Jacob Collier. And Beyoncé, the most nominated woman in the history of the Grammys, won her 24th award.
Nipsey Hussle, who will be honored during the live telecast which begins at 8 p.m. Eastern, has posthumously won best rap performance for "Racks in the Middle," which features Roddy Ricch and Hit-Boy.
Hussle's family, including his brother, grandmother and actress-fiancée Lauren London, accepted the honor during the pre-telecast.
"Nip did it, not just for the awards, but for the people," London said onstage.
Hussle was nominated for two other awards: He lost best rap song to J. Cole and 21 Savage. The third award will be presented during the live show, where Hussle will be honored with a tribute performance from DJ Khaled, John Legend, Meek Mill and others.
The pre-telecast ceremony, where most of the awards are handed out, opened with a brief remembrance of NBA star Kobe Bryant, who was killed earlier in the day in a helicopter crash in California.
Referring to the arena where Bryant played for the Los Angeles Lakers, Interim Recording Academy CEO Harvey Mason Jr. said, "Since we are in his house, I would ask you to join me in a moment of silence."
New stars like Lizzo, Eilish and Lil Nas X — the most-nominated acts Sunday — won their first Grammys of their careers and have chance to win more, though a cloud loomed over this year's awards.
Ten days before arguably the biggest night in music, the industry erupted when the Recording Academy announced it had put its recently hired CEO, Deborah Dugan, on administrative leave for misconduct. Dugan and her lawyers fired back at the academy, claiming that the awards show is rigged.
Tarriona "Tank" Ball of the New Orleans soul-funk band Tank and the Bangas, nominated for best new artist, said she's not letting the drama ruin the achievement for her band.
"I feel like I'm exactly where I'm supposed to be at, and I don't want anything taking away from all the nominees," Ball said. "This is our moment. This is our time."
Sunday's Grammys are airing live from the Staples Center in Los Angeles starting at 8 p.m. Eastern. The show will be jam-packed with performances, including Ariana Grande, BTS, Camila Cabello, Demi Lovato, Jonas Brothers, Rosalia, Aerosmith, Bonnie Raitt, Tyler, the Creator, Gwen Stefani, Blake Shelton, John Legend and Cyndi Lauper.
The show will also include special tributes to Prince and longtime Grammys producer Ken Ehrlich, who is wrapping up his career with the show Sunday.
Lizzo, who walked into the show the most nominated with eight, will also perform.
Her major-label debut, "Cuz I Love You," is nominated for album of the year along with projects from Grande, Lana Del Rey, Vampire Weekend, H.E.R., Bon Iver, Eilish and Lil Nas X.
Lizzo's No. 1 hit, "Truth Hurts," is also up for song and record of the year. Eilish, who will perform, also scored song and record of the year nods for her No. 1 hit, "Bad Guy."
Other record of the year nominees include Lil Nas X's "Old Town Road," Grande's "7 Rings," Post Malone and Swae Lee's "Sunflower," H.E.R.'s "Hard Place," Bon Iver's "Hey, Ma" and Khalid's "Talk."
Taylor Swift was shut out of album and record of the year, but she did score a nod for song of the year — a songwriter's award. Her tune "Lover" is nominated against "Truth Hurts," "Bad Guy," "Hard Place," Gaga's "Always Remember Us This Way" from "A Star Is Born," Lewis Capaldi's "Someone You Loved," Lana Del Rey's "Norman (Expletive) Rockwell" and Tucker's "Bring My Flowers Now," which was co-written by Brandi Carlile.
The Grammys will hand out roughly 10 awards during the live show. Presenters this year include Stevie Wonder, Smokey Robinson, Billy Porter, Trevor Noah, Ozzy and Sharon Osbourne, Cynthia Erivo, Ava DuVernay, Shania Twain and Common.