Intended by lyricist Hal David to convey a woman's concern for her man who's serving in the Vietnam War, "I Say a Little Prayer" was recorded by Dionne Warwick in a 9 April 1966 session. Although Bacharach's recordings with Warwick typically took no more than three takes (often only taking one), Bacharach did ten takes on "I Say a Little Prayer" and still disliked the completed track feeling it rushed. The track went unreleased until September 1967 when it was introduced on the album The Windows of the World which largely consisted of older material; it was Scepter Records owner Florence Greenberg rather than Bacharach who wanted "I Say a Little Prayer" added to that album  from which it had a single release in October 1967 as the intended B-side of the newly recorded track "(Theme from) Valley of the Dolls". However, the brisk sound of "I Say a Little Prayer" which Bacharach disliked proved to be the comeback sound for Warwick as "I Say a Little Prayer" became the original favored side reaching #4 that December on the Billboard Hot 100 – Warwick's first Top Ten appearance since "Message to Michael" in the spring of 1966 – and also #8 on the Billboard R & B Chart and #4 on the Canadian Charts. "(Theme from) Valley of the Dolls" would become a hit subsequent to the success of "I Say a Little Prayer" reaching #2 in February 1968: Warwick's "I Say a Little Prayer"/"(Theme from) Valley of the Dolls" single would receive gold certification from the RIAA for sales of a million units becoming the only certified gold single of the first phase of Warwick's career.
"I Say a Little Prayer" b/w "(Theme from) Valley of the Dolls", became one of the most successful double-sided hits of the Rock era. Like several Bacharach compositions, both sides contains passages written in unusual time signatures. The verses of "Prayer" are constructed of 2 successive measures of 4/4, a measure of 10/4 (using 4/4 + 2/4 + 4/4), and 2 final measures of 4/4. The chorus is in 11/4 (using 4/4 + 3/4 + 4/4), played by session drummer Gary Chester.
Warwick's "I Say a Little Prayer" did not appear on the Billboard Easy Listening chart although two instrumental versions of the song were Easy Listening chart items in 1968: the first by Sérgio Mendes at No. 21 in the spring of 1968 while that fall Julius Wechter and the Baja Marimba Band took "I Say a Little Prayer" to No. 10 Easy Listening.
"I Say a Little Prayer" also returned to the Pop & R&B Top Ten in the fall of 1968 via a recording by Aretha Franklin taken from her 1968 Aretha Now album. Franklin and background vocalists the Sweet Inspirations were singing the song for fun while rehearsing the songs intended for the album when the viability of Franklin actually recording "I Say a Little Prayer" became apparent, significantly re-invented from the format of the Dionne Warwick original via the prominence of Clayton Ivey's piano work and the choral vocals of the Sweet Inspirations. Similar to the history of Warwick's double-sided hit, the Aretha Franklin version was intended as the B-side of the July 1968 single release "The House that Jack Built" but began to accrue its own airplay that August. Even with "The House That Jack Built" ranking as high as No. 6 (#2 R&B) in September 1968, "I Say a Little Prayer" reached No. 10 (#3 R&B) that October, the same month the single was certified Gold by the RIAA. "Prayer" became Franklin's ninth and last consecutive Hot 100 top 10 hit on the Atlantic label (not counting every flip side), with each of the nine curiously peaking at a different position. Franklin's "Prayer" has a special significance in her UK career, as with its September 1968 No. 4 peak it became Franklin's biggest UK hit; subsequently Franklin has surpassed that track's UK peak only with her No. 1 collaboration with George Michael, "I Knew You Were Waiting (For Me)". In February 1987, UK music weekly New Musical Express published its critics' top 150 singles of all time, with Franklin's "I Say a Little Prayer" ranked at No. 1, followed by Al Green's "Tired of Being Alone" and Warwick's "Walk On By". (Franklin's "I Say a Little Prayer" did not appear in the magazine's in-house critics' top 100 singles poll conducted in November 2002.)
In Australia, "I Say a Little Prayer" and "The House That Jack Built" were assigned a joint chart ranking which saw the double-A-side hit reach No. 10 in November 1968. "I Say a Little Prayer" also gave Franklin a European hit with chartings in France (#12), Germany (#29) and the Netherlands (#4).
The 1971 album Anne Murray / Glen Campbell features a medley of "I Say a Little Prayer" and "By the Time I Get to Phoenix"; the songs are sung in counterpoint to each other, with Murray vocalizing on "I Say a Little Prayer" while Campbell reprises his "By the Time I Get to Phoenix" hit. The track was a minor C&W hit at No. 40 and reached No. 81 on the Billboard Hot 100. The concept had previously been used on a 1968 single release by Big Dee Irwin and Mamie Galore and was subsequently reworked when Dionne Warwick herself sang "I Say a Little Prayer" while Isaac Hayes sang "By the Time I Get to Phoenix" on their joint live album A Man and a Woman (1977).
The song is also a popular soundtrack item: in the 1969 comedy The April Fools, for which Warwick sang the title song, "I Say a Little Prayer" is performed at a swanky house party in a live performance by singer Susan Barrett. "I Say a Little Prayer" is one of several Bacharach/David songs featured prominently in the comedy My Best Friend's Wedding in 1997, which featured both a reggae-style cover by Diana King and a version sung by the film's cast. King's version was released as a single and brought the song back to the Top 40 almost thirty years after Dionne Warwick's original, albeit with a No. 38 peak; King's single also reached No. 38 in France. Cassie Henderson, 14, sung this song for Soul Week on The X-Factor NZ Season 1 Episode 16. A parody of the song with altered lyrics was featured in the 2006 comedy film Date Movie making fun of its use in My Best Friend's Wedding.