When Austin was four years old, she performed at the Apollo Theater. As a teenager she recorded commercial jingles and worked as a session singer in soul and R&B. She had an R&B hit in 1969 with “Family Tree”. She sang backing vocals on Paul Simon’s 1975 number-one hit “50 Ways to Leave Your Lover”. The jazz label CTI released her debut album, End of a Rainbow, in 1976. She sang “The Closer I Get to You” for Tom Browne’s album Browne Sugar, a duet with Michael Jackson for his album Off the Wall, and a duet with George Benson on “Moody’s Mood for Love”. After singing on Quincy Jones’s album The Dude, she signed a contract with his record label, Qwest, which released Every Home Should Have One with “Baby, Come to Me”, a duet with James Ingram that became a No. 1 hit on the Billboard magazine pop chart. A second duet with Ingram, “How Do You Keep the Music Playing”, appeared on soundtrack to the movie Best Friends (1982). GRP released her album Love Is Gonna Getcha, which contained the singles “Good in Love” and “Through the Test of Time”.

In 2000 she performed with the WDR Big Band. Her album The Real Me contained versions of jazz standards, while For Ella was a tribute to jazz singer Ella Fitzgerald. In 2003, she collaborated with Frances Yip on Papillon III in the rotunda of San Francisco City Hall to help the Jade Ribbon Campaign of Stanford University. A companion CD/DVD was released with Austin and Yip singing duets in Mandarin.

Austin was booked for United Flight 93 on September 11, 2001, but because her mother suffered a stroke days before, she cancelled her ticket and flew at a different time.

During a 2007 interview, Austin spoke of reluctantly attending as a teenager one of Judy Garland’s last concerts and how the experience helped focus her career. “She ripped my heart out. I wanted to interpret a lyric like that, to present who I was at the moment through the lyric.”

In 2011, Sound Advice was released containing cover versions of Bob Dylan’s “Gotta Serve Somebody”, Brenda Russell’s “A Little Bit of Love”, the Jackson Five’s “Give It Up”, Bill Withers’ “Lean on Me”, and Don McLean’s “Vincent”. The album also included “The Grace of God”, a song Austin wrote after watching an episode of the Oprah Winfrey Show which included a woman with scarred face. Austin appeared in the documentary film 20 Feet from Stardom, which premiered at the Sundance Film Festival and was released on 21 June 2013.

In 2015, Austin appeared on Patrick Williams’ Home Suite Home large jazz ensemble album, as vocalist for Williams’ composition “52nd & Broadway,” which won a Grammy for Best Arrangement, Instruments and Vocals.

On June 25, 2019, The New York Times Magazine listed Patti Austin among hundreds of artists whose material was destroyed in the 2008 Universal fire.