Lady Gaga, who was up for six awards, continued her homage to Pop Queen Madonna - her latest single sounded similar to Madonna's "Express Yourself."
Gaga thanked all her fans and "all the monsters" from the bottom of her heart.
She also thanked Whitney Houston, for being the inspiration for "Born This Way."
She said she imagined Houston singing it because she "wasn't secure enough to imagine" herself as a superstar.
Teen sensation Justin Bieber's journey to stardom was revisited by a video showing his meeting with Usher.
Nicely timed with the release of the documentary about his rise to fame, Bieber performed "Never Say Never" with a group of dancers dressed in ninja-style attire.
Mid-point during his performance, "J-Smith" or Jaden Smith the son of actor Will Smith and actress Jada Pinkett Smith appeared on stage to sing along with Bieber.
Usher later returned to stage to perform with Bieber and showed off their smooth dance skills.
The show-stopping performance received a standing ovation from the audience.
But perhaps the most colorful performance that topped the night came from Gwyneth Paltrow and Gnarls Barkley frontman Cee Lo Green.
On stage, they sang his Grammy-nominated hit record "F--- You." They were joined by Jim Henson Company Puppets.
Green was decked out in a costume made of peacock feathers while Paltrow was dressed in a black jumpsuit.
Paltrow first sang a toned-down version of the song on the show "Glee."
They may be topping the charts right now, but they weren't too big to salute their elders. Mick Jagger appeared on the Grammy stage for the first time in his 50-year career.
Streisand conquered her stage fright to perform "Evergreen," after being introduced by another music legend, her "A Star Is Born" co-star Kris Kristofferson.
Meanwhile, music icon Bob Dylan, a 10-time Grammy and lifetime achievement winner, joined Mumford & Sons and The Avett Brothers for a salute to acoustic music.
Rap legend Dr. Dre gave his first performance on live television in a decade.
He was joined by his protege Eminem, who was up for album of the year for "Recovery," which earned the rapper a leading 10 nominations. Maroon 5's Adam Levine also performed with Eminem.
Rihanna dressed in a flowing black and gold dress, opened the set with Eminem appearing moments later to sing "Love the Way You Lie."
"Power trio" Bruno Mars, B.o.B. and Janelle Morae shared the stage to perform some of their most popular songs.
B.o.B. opened the set with "Nothin' on You."
Bruno Mars sang "Grenade" in a throwback to James Brown and Monae serenaded the audience with "Cold War."
Rihanna returned to the stage later in the show to perform her song "What's My Name?" with Drake.
The cast of "Glee" was up for two awards.
Their first album, "Glee: The Music, Volume 1," was up for best compilation soundtrack album for motion picture, television or other visual media. But the real surprise was being nominated for best pop performance by a duo or group with vocals for their rendition of Journey's "Don't Stop Believin.'"
They were competing against Maroon 5, Paramore, Sade and Train.
However, Train took home the award for best pop performance by a duo or group.
"Thanks, Justin Bieber, for not being a duo or group," joked Patrick Monahan, Train's lead singer as he accepted the first award of the night.
ABC News Radio's Christopher Watson, Shane Lou and the Associated Press contributed to this story.