Tony! Toni! Toné! would become major R&B superstars throughout the late-1980s and 1990s. However, after the 1996 album entitled House of Music failed to duplicate the group's previous success, Tony! Toni! Toné! went their separate ways in 1997.

He has been playing the bass guitar since the age of six, and first began singing at age nine in a local gospel group. At the age of 12, he joined a group called "The Gospel Humminbirds". In 1984, shortly before his 18th birthday, Saadiq heard about tryouts in San Francisco for Sheila E.'s backing band on Prince's Parade Tour. At the audition, he chose the name "Raphael", and had difficulty remembering to respond to the name when he heard that he got the part to play bass in the band. He says of the experience, "Next thing I was in Tokyo, in a stadium, singin' Erotic City. We were in huge venues with the biggest sound systems in the world; all these roadies throwin' me basses, and a bunch of Models hangin' round Prince to party. For almost two years. That was my university."

After returning to Oakland from touring with Prince, Saadiq began his professional career as the lead vocalist and Bassist in the rhythm and blues and dance trio Tony! Toni! Toné! He used the name Raphael Wiggins while in Tony! Toni! Toné!, along with his brother Dwayne Wiggins, and his cousin Timothy Christian. In the mid-1990s, he adopted the last name Saadiq, which means "man of his word" in Arabic. His change of surname led many to speculate that he had converted to Islam at that point; in reality, Saadiq is not a Muslim, but rather just liked the way "Saadiq" sounded and changed his last name simply to distinguish himself from and avoid potential confusion with his brother, Dwayne Wiggins. As he confirmed by telling noted R&B Writer Pete Lewis of the award-winning 'Blues & Soul' in May 2009, "I just wanted to have my own identity!"

In 1995, Saadiq had his biggest solo hit to date, when "Ask of You", featured on the Higher Learning Soundtrack peaked at #19 on the Billboard Hot 100 and #2 on the R&B chart. In 1995, Saadiq produced and performed on Otis & Shug's debut album, We Can Do Whatever.

Also in 1999, he collaborated with Rapper Q-Tip on the single "Get Involved", from the animated television series The PJs. It samples The Intruders' 1973 song "I'll Always Love My Mama" and charted at number 21 on the US Hot R&B/Hip-Hop Singles & Tracks.

His 2000 song collaboration "Untitled (How Does It Feel)" won D'Angelo a Grammy Award for Best Male R&B Vocal Performance; it was also nominated for Grammy Award for Best R&B Song. The song was ranked #4 on Rolling Stone's "End of Year Critics & Readers Poll" of the top singles of 2000. D'Angelo's album Voodoo won a Grammy Award for Best R&B Album at the 2001 Grammy Awards.

In 2002, Saadiq founded his own record label, Pookie Entertainment. Among the artists on the label are Joi and Truth Hurts. In 2002, he released his first solo album Instant Vintage, which earned him five Grammy Award nominations. He released a two-disc live album All the Hits at the House of Blues in 2003, and his second studio album Ray Ray in 2004, both on Pookie Entertainment.

In 2004, Saadiq produced a remix of the song "Crooked Nigga Too" by Tupac Shakur which is featured on the album Loyal to the Game. Other artists he has collaborated with include Whitney Houston, Mary J. Blige, The Isley Brothers, A Tribe Called Quest, Teedra Moses, The Roots, Erykah Badu, Jill Scott, Macy Gray, Angie Stone, Snoop Dogg, Mac Dre, Devin the Dude, DJ Quik, Kelis, Q-Tip, Lil' Skeeter, Ludacris, The Bee Gees, Musiq Soulchild, Jaguar Wright, Chanté Moore, Lionel Richie, Marcus Miller, Noel Gourdin, Nappy Roots, Calvin Richardson, T-Boz from TLC, Jody Watley, Floetry, Leela James, Amp Fiddler, John Legend, Joss Stone, Young Bellz, Anthony Hamilton, Babyface, Ledisi, Goapele, Ghostface Killah, —Ginuwine, The Grouch Stevie Wonder, Earth, Wind & Fire, Bilal, Chali 2na, Larry Graham, Luniz as well as many others. In 2007, Saadiq produced Introducing Joss Stone, the third album of British soul singer Joss Stone. According to J. Gabriel Boylan of The New York Observer, "he's produced artists including Macy Gray, the Roots, D'Angelo, John Legend, Whitney Houston, Mary J. Blige, and more. With all of them he's pushed a classic aesthetic, heavy on organic sounds and light on studio magic, deeply indebted to the past and distrustful of easy formulas."

Saadiq's third solo album, The Way I See It, released on Columbia Records on September 16, 2008, available in a collector's edition box set of 7" 45 rpm singles as well as on traditional CD, was critically well-received, made several critics' 2008 best albums lists, and garnered three Grammy nominations including Best R&B Performance by a Duo Or Group With Vocals (for "Never Give You Up", featuring Stevie Wonder & CJ Hilton); Best Traditional R&B Vocal Performance (for "Love That Girl") and Best R&B Album for The Way I See It. Music from The Way I See It was featured in the following motion pictures: Madea Goes To Jail, Bride Wars, Cadillac Records, Secret Life of Bees, In Fighting (Rogue), and It's Complicated.

He produced songs for LeToya Luckett's forthcoming second album Lady Love, released August 2009. In 2009, Saadiq produced "Please Stay" and "Love Never Changes" for Ledisi's August 2009 release "Turn Me Loose". Saadiq also was the executive Producer for an emerging group called Tha Boogie. Tha Boogie's first EP was released on iTunes and is titled Love Tha Boogie, Vol. 1 (Steal This Sh*t).

In 2009, Saadiq announced his video game development company called IllFonic. The first video game in development by IllFonic is titled Ghetto Golf, with an expected release late in 2010. In 2009, Saadiq teamed up Bentley Kyle Evans, Jeff Franklin, Martin Lawrence, and Trenten Gumbs to create a new sitcom called Love That Girl! starring Tatyana Ali. Raphael is an executive Producer and Composer for Love That Girl!. The show airs on TV One and debuted on January 19, 2010. That same year, Saadiq performed The Spinners hit "It's A Shame" in a legendary Levi's commercial and sang as part of the chorus in the 2010 remake of "We Are the World" for Haiti.

In fall 2011, he performed on the fourth results show of Dancing with the Stars season 13. In December 2011, he performed a cover compilation of several Neil Diamond songs at the Kennedy Center Honors award ceremony.

In 2012 he signed a deal with Toyota to do a TV commercial for the Toyota Prius. In 2013 Raphael partnered with Bay Area/ Atlanta Production company EL Seven Entertainment/ Republic Records and new R&B Superstar Adrian Marcel and released his 1st promotional mixtape "Raphael Saadiq Presents Adrian Marcel 7 Days of Weak".

Saadiq is a featured bass guitar player on Elton John's 2013 album, The Diving Board.

In 2016 he executive produced Solange Knowles album, A Seat At The Table which debuted at #1 on music charts in the United States. He also guest starred in Luke Cage, where he performs his songs "Good Man" and "Angel" at Harlem's Paradise.

In 2017 he appeared in the award-winning documentary film The American Epic Sessions, directed by Bernard MacMahon, where he recorded the Memphis Jug Band’s 1928 song “Stealin’ Stealin’” live on the restored first electrical sound recording system from the 1920s. Of recording on the system he said, “it’s amazing to just look at how it’s built, you know just look at the machine itself. It just has this like magical sound the way that it’s built. It’s true. It’s just the truest sound you could ever get.”