After an unsuccessful debut album, he took the powerful ballad "Mandy" to number 1 in America. The song had previously been a UK hit for its co-writer Scott English, as "Brandy". This was the prelude to 10 years of remarkable hit parade success. With his strong, pleasant tenor, well-constructed love songs and ingratiating manner in live shows, Manilow was sneered at by critics but adored by his fans, who were predominantly female. Among the biggest hits were "Could It Be Magic" (1975), "I Write The Songs" (composed by the Beach Boys' Bruce Johnston (1976), "Tryin' To Get The Feeling Again" (1976), "Looks Like We Made It" (1977), "Can't Smile Without You" (1978), the upbeat "Copacabana (At The Copa)" (1978), "Somewhere In The Night" (1979), "Ships" (1979), and "I Made It Through The Rain" (1980).

Two albums, 2:00 AM Paradise Caf, and Swing Street, marked a change of direction as Manilow underlined his jazz credentials in collaborations with Gerry Mulligan and Sarah Vaughan. He also appeared on Broadway in two one-man shows, the second of which, Showstoppers (1991), was a schmaltzy tribute to great songwriters of the past. During the 80s, Manilow was invited by the widow of one of those writers, Johnny Mercer, to set to music lyrics unpublished during Mercer's lifetime. A selection of these were recorded by Nancy Wilson on her 1991 album With My Lover Beside Me. In June 1994, the stage musical Copacabana, for which Manilow composed the music and co-wrote the book, opened in London starring Gary Wilmot and Nicola Dawn. In the same year he was the supervising composer, and collaborated on several of the songs, for the animated feature Thumbelina. His last album for Arista was a strongly jazz flavored recording on which he sang Sinatra classics. It was no great surprise that he signed to Concord Jazz the following year. In 2001 a candid and revealing biography written by Patricia Butler was published.

Manilow's "Copacabana" has also been turned into a stage musical; which toured in 2003.

Manilow appeared as a guest judge and even arranged music for American Idol on April 24, 2004, the year in which he also embarked on his "One Night Live! One Last Time!" final tour. Some fans were unhappy that Manilow charged his fans $1000 to meet him after the show for charity. Critics are not uniformly impressed by the tour, either, noting that the name of the tour suggests that he should be emphasizing his repertoire of Top 40 hits, instead of kitschy Broadway-style production numbers, and an apparently rather notorious crotch-grabbing gesture during the performance of Copacabana.

Although not all Manilow's hits were written by him (the most notable instance, ironically, being "I Write The Songs", actually written by lyricist Bruce Johnston), he co-wrote, with lyricist Bruce Sussman, a musical, Harmony, which was originally to have been produced in Philadelphia during 2003. After financial difficulties and a legal battle, Manilow and Sussman won back the rights to the musical which is now to be produced on stage in 2005.