After his graduation from Rumson High School, Riddle spent his late teens and early 20s playing trombone in and occasionally arranging for various local dance bands, culminating in his association with the Charlie Spivak Orchestra. In 1943, Riddle joined the Merchant Marine, serving at Sheepshead Bay, Brooklyn, New York for about two years while continuing to work for the Charlie Spivak Orchestra.

Riddle studied orchestration under his fellow merchant mariner, composer Alan Shulman. After his enlistment term ended, Riddle traveled to Chicago to join Tommy Dorsey’s orchestra in 1944, where he remained the orchestra’s third trombone for eleven months until drafted by the Army in April 1945, shortly before the end of World War II. He was discharged in June 1946, after fifteen months of active duty. He moved shortly thereafter to Hollywood to pursue a career as an arranger, and spent the next several years writing arrangements for multiple radio and record projects. In May 1949, Doris Day had a #2 hit, “Again”, backed by Riddle.

Riddle married his first wife, Doreen Moran, in 1945, while in the Army. The couple had six children. Riddle had an extra-marital affair with singer Rosemary Clooney in the 1960s, which contributed to the breakup of their respective marriages. In 1968, Riddle separated from his wife Doreen; their divorce became official in 1970. A few months later he married Naomi Tenenholtz, then his secretary, with whom he would remain for the rest of his life. Riddle’s children are dispersed between the east and west coasts of the United States, with Nelson Jr. residing in London, England and married to British actress Paula Wilcox. Riddle’s eldest daughter, Rosemary, is the trustee of the Nelson Riddle Trust.

In 1950, Riddle was hired by composer Les Baxter to write arrangements for a recording session with Nat King Cole; this was one of Riddle’s first associations with Capitol Records. Although one of the songs Riddle had arranged, “Mona Lisa,” soon became the biggest selling single of Cole’s career, the work was credited to Baxter. However, once Cole learned the identity of the arrangement’s creator, he sought out Riddle’s work for other sessions, and thus began a fruitful partnership that furthered the careers of both men at Capitol.

In 1953, Capitol Records executives viewed the up-and-coming Riddle as a prime choice to arrange for the newly arrived Sinatra. Sinatra was reluctant however, preferring instead to remain with Axel Stordahl, his long-time collaborator from his Columbia Records years. When success of the first few Capitol sides with Stordahl proved disappointing, Sinatra eventually relented and Riddle was called in to arrange his first session for Sinatra, held on April 30, 1953. The first product of the Riddle-Sinatra partnership, “I’ve Got the World on a String”, became a runaway hit and is often credited with relaunching the singer’s slumping career. Riddle’s personal favorite was a Sinatra ballad album, one of his most successful recordings, Only the Lonely.

For the next decade, Riddle continued to arrange for Sinatra and Cole, in addition to such Capitol artists as Kate Smith, Judy Garland, Dean Martin, Keely Smith, Sue Raney, and Ed Townsend. He also found time to record his own instrumental discs, released on Capitol in both 45 RPM single, and LP album format. Riddle’s most successful tune was “Lisbon Antigua”, released in November 1955, which reached and remained at the #1 position for four weeks in 1956. Riddle’s most notable LPs were Hey … Let Yourself Go (1957) and C’mon … Get Happy (1958), both of which peaked at a respectable number twenty on the Billboard charts. In 1959, he won the Grammy Award for Best Musical Composition First Recorded and Released in 1958 (over 5 minutes duration) at the inaugural award ceremony for Cross Country Suite.

In 1957, Riddle and his orchestra were featured on The Rosemary Clooney Show, a 30-minute syndicated program.

In 1962, Riddle orchestrated two albums for Ella Fitzgerald, Ella Swings Brightly with Nelson, and Ella Swings Gently with Nelson, their first work together since 1959’s Ella Fitzgerald Sings the George and Ira Gershwin Song Book. The mid-1960s would also see Fitzgerald and Riddle collaborate on the last of Ella’s Songbooks, devoted to the songs of Jerome Kern (Ella Fitzgerald Sings the Jerome Kern Song Book) and Johnny Mercer (Ella Fitzgerald Sings the Johnny Mercer Song Book).

In 1963, Riddle joined Sinatra’s newly established label Reprise Records, under the musical direction of Morris Stoloff.

In 1966, Riddle was hired by television producer William Dozier to create the music for the Batman television series starring Adam West. (Neal Hefti had written the Batman theme song and was originally hired for the series, but became unavailable.) Riddle did the first two seasons of Batman (sans two episodes scored by Warren Barker). Billy May did the third season’s music. Re-recordings of Riddle’s music from Batman were issued on one soundtrack LP and a 45 RPM single. There was a “Batmanesque” tone in the soundtrack for Howard Hawks’ John Wayne film El Dorado, also scored by Riddle in 1966, due to his continued heavy use of brass.

In the latter half of the 1960s, the partnership between Riddle and Frank Sinatra grew more distant as Sinatra began increasingly to turn to Don Costa, Billy May and an assortment of other arrangers for his album projects. Although Riddle would write various arrangements for Sinatra until the late 1970s, Strangers In The Night, released in 1966, was the last full album project the pair completed together. The collection of Riddle-arranged songs was intended to expand on the success of the title track, which had been a number one hit single for Sinatra arranged by Ernie Freeman.

Riddle’s film and television work in the 60s included his hit theme song for Route 66, the theme to The Untouchables, and the scores for the Rat Pack motion pictures Robin and the 7 Hoods and the original Ocean’s 11. In 1969, he arranged and conducted the music to the film Paint Your Wagon, which starred a trio of non-singers, Lee Marvin, Clint Eastwood, and Jean Seberg.

During the 1970s, Riddle’s film and television efforts included the score for the 1974 version of The Great Gatsby, which earned him his first Academy Award, after some five nominations. In 1973, he served as musical director for the Emmy Award winning The Julie Andrews Hour. He wrote the theme song for the 1972 television series Emergency!, and scored the 1977 miniseries Seventh Avenue. The Nelson Riddle Orchestra also made numerous concert appearances throughout the 1970s, some of which were led and contracted by his good friend, Tommy Shepard.

On March 14, 1977, Riddle conducted his last three arrangements for Sinatra. “Linda”, “Sweet Lorraine”, and “Barbara”, were intended for an album of songs with women’s names. The album was never completed. “Sweet Lorraine” was released in 1990 and the other two were included in The Complete Reprise Studio Recordings, released in 1995.

1982 saw Riddle work for the last time with Ella Fitzgerald, on her last orchestral Pablo album, The Best Is Yet to Come.

In a 1982 radio interview on WNEW with Jonathan Schwartz, Riddle cited Stan Kenton’s “23 Degrees North, 82 Degrees West” arranged by Bill Russo as inspiration for his signature trombone interplay crescendos.

In the spring of 1982, Riddle was approached by Linda Ronstadt — via telephone through her manager and producer, Peter Asher — to write arrangements for an album of jazz standards that Linda had been contemplating since her stint in The Pirates of Penzance. The agreement between the two resulted in a three-album contract which included what were to be the last arrangements of Riddle’s career, with the exception of an album of twelve Great American Songbook standards he arranged and conducted for his old friend, opera singer Kiri Te Kanawa, in April 1985, six months before his death that October. Ronstadt recalls that when she initially approached Riddle, she did not know if he was even familiar with her music. He knew her name, but basically hated rock ‘n’ roll. However, his daughter was a big Linda Ronstadt fan and told her father, “Don’t worry, Dad. Her checks won’t bounce.”

On January 19, 1985, Riddle conducted at the nationally televised 50th Presidential Inaugural Gala, the day before the second inauguration of Ronald Reagan. The program was hosted by Frank Sinatra, who sang “Fly Me to the Moon” and “One for My Baby (and One More for the Road)” (backed by a solo dance routine by Mikhail Baryshnikov).

In 1985, Riddle died in Los Angeles, at Cedars-Sinai Medical Center, at age 64 of cardiac and kidney failure as a result of cirrhosis of the liver, with which he had been diagnosed five years earlier. His cremated remains are inurned at Hollywood Forever Cemetery in Hollywood, California in the Hall of David Mausoleum.

Following Riddle’s death, his last three arrangements for Ronstadt’s For Sentimental Reasons album were conducted by Terry Woodson; the album was released in 1986. In February 1986, Riddle’s youngest son Christopher, himself an accomplished bass trombonist, assumed the leadership of his father’s orchestra. Following the death of Riddle’s second wife Naomi in 1998, proceeds from the sale of the Riddle home in Bel Air were used to establish a Nelson Riddle Endowed Chair and library at the University of Arizona, which officially opened in 2001. The opening showcased a gala concert of Riddle’s works, with Ronstadt as a featured guest performer. In 2000, Erich Kunzel and the Cincinnati Pops released a Nelson Riddle tribute album on Telarc Records titled Route 66: That Nelson Riddle Sound. The album showcased expanded orchestral adaptations of the original arrangements provided by the Nelson Riddle Archives, and was presented in a state-of-the-art digital recording that was among the first titles to be released on multi-channel SACD.