The Righteous Brothers started their career on Moonglow with two moderate hits: "Little Latin Lupe Lu" and "My Babe" in 1963, as well as two albums. Both songs received airplay, but their first major hit single was "You've Lost That Lovin' Feelin'" on the Philles label in 1965. Produced by Phil Spector, the record is often cited as one of the peak expressions of Spector's Wall of Sound production techniques. It was one of the most successful pop singles of its time, despite exceeding the standard length for radio play. Indeed, according to BMI, "You've Lost That Lovin' Feelin'" remains the most played song in radio history, estimated to have been broadcast more than eight million times. It is also well known as an unofficial Nottingham Forest UK football club anthem, often sung to opposition fans after Forest have scored a goal. A little known fact is that Spector used Cher (of Sonny & Cher fame) as a backup singer on this and other recordings (also little known is that they were never actually signed to Philles; they were still under contract to Moonglow and Spector leased their contract).

The Righteous Brothers had several other Spector-produced hit singles in 1965, including "Just Once in My Life," "Unchained Melody" (a Hatfield solo that originally was the B-side of "Hung on You"), and "Ebb Tide". However, they did not get along with Spector, and at the same time Spector had lost interest in the act and sold their contract to Verve/MGM Records in 1965. They next released "(You're My) Soul and Inspiration" (a Phil Spector sound-alike song, produced by Bill Medley, who was able to simulate the Spector style of production) on Verve, which became a #1 hit in 1966. After a few more top 40 songs, including their renditions of "White Cliffs of Dover" and "Georgia on My Mind", their popularity began to decline, perhaps because older recordings were being released by Moonglow during the time they were enjoying popularity with Philles (1964-65) and Verve (1966-67). They eventually split up for more than seven years.

Medley recorded a few solos including "Brown-Eyed Woman" (1968). Bobby Hatfield teamed up briefly with another singer, Jimmy Walker (drummer and one of the singers of the Knickerbockers, of "Lies" fame), using the Righteous Brothers name, but neither he nor Hatfield was able to achieve any significant level of success. In 1974, Medley and Hatfield reunited, performing on the Sonny and Cher Hour.

In 1974, they signed with Haven Records, run by producers Dennis Lambert and Brian Potter, and distributed by Capitol Records. They scored another hit with the Lambert/Potter produced "Rock and Roll Heaven", a paean to several deceased rock singers; Janis Joplin, Jimi Hendrix, Jim Morrison, Otis Redding, Jim Croce and Bobby Darin are among those mentioned (Croce and Darin died within three months of each other in late 1973, shortly before the song was released): it peaked at #3 on the Billboard charts. It was updated in 1990 to reflect the deaths of Elvis Presley, Marvin Gaye, Jackie Wilson, Dennis Wilson, John Lennon and Roy Orbison. A few more minor hits on Haven followed, and then the Righteous Brothers found themselves "hitless" again until 1990, although they toured frequently. Medley also had solo success: In 1984, he scored country hits with "Till Your Memory's Gone" and "I Still Do" (which crossed over to the adult contemporary charts and later became a "cult" hit with the Carolina Beach/Shag dance club circuit); and in late 1987, his duet with Jennifer Warnes — "(I've Had) The Time of My Life", which appeared on the soundtrack for Dirty Dancing — topped the Billboard Hot 100 and earned a Grammy Award. He also scored a moderate UK hit in 1988 with a version of "He Ain't Heavy, He's My Brother". One of Medley's minor entries, "Don't Know Much", was a #2 hit in late 1989 as a duet by Linda Ronstadt and Aaron Neville.

In 1990 the original recording of "Unchained Melody" was featured in the hit Patrick Swayze movie "Ghost" and caused an avalanche of requests to Top 40 radio by fans who had seen the movie, which motivated Polygram (who now owned the Verve/MGM label archives) to re-release the song to Top 40 radio where it became a Top 40 hit for a second time. The brothers quickly re-recorded a cover version for Curb Records which also made the charts.

The Righteous Brothers were inducted into the Rock and Roll Hall of Fame on March 10, 2003.

In 2008, The Righteous Brothers 21st Anniversary television special, filmed at the Roxy on the Sunset Strip in Los Angeles in 1983, aired on numerous Public Television stations throughout the United States.

Bobby Hatfield was found dead in his hotel room in Kalamazoo, Michigan on November 5, 2003, half an hour before he was due to perform a concert with Bill Medley at Western Michigan University's Miller Auditorium. His death was caused by cocaine and not simply heart failure, as was initially suspected, according to the official autopsy report.