Ashford was born in Fairfield, South Carolina, and Simpson in the Bronx, New York. Afterwards, his family relocated to Ypsilanti, Michigan, where he became a member of Christ Temple Baptist Church. While there, he sang with a group called The Hammond Singers (named after the founding minister, James Hammond). Later, Nickolas attended and graduated from Willow Run High School in Ypsilanti, Michigan, before pursuing his professional career, where he would ultimately meet his wife, Valerie. They met at Harlem's White Rock Baptist Church in 1964. After having recorded unsuccessfully as a duo, they joined an aspiring solo artist and former member of the Ikettes, Joshie Jo Armstead, at the Scepter/Wand label, where their compositions were recorded by Ronnie Milsap ("Never Had It So Good"), Maxine Brown ("One Step at a Time"), as well as the Shirelles and Chuck Jackson. Another of the trio's songs, "Let's Go Get Stoned", gave Ray Charles a number one U.S. R&B hit in 1966. That same year, Ashford & Simpson joined Motown, where their best-known songs included "Ain't No Mountain High Enough", "You're All I Need To Get By", "Ain't Nothing Like the Real Thing", and "Reach Out and Touch (Somebody's Hand)". Ashford and Simpson wrote many other hit songs, including Chaka Khan's "I'm Every Woman" (1978) and Teddy Pendergrass's "Is It Still Good to You?".
As performers, Ashford & Simpson's best-known duets are "Solid" and "Found a Cure" (1979). The duo was inducted into the Songwriters Hall of Fame in 2002. Ashford and Simpson were also recipients of The Rhythm & Blues Foundation's Pioneer Award in 1999, and ASCAP's highest honor, the Founder's Award, which they received on March 18, 1996.