The song was released as the lead single from Enya's second studio album, Watermark, in October 1988. It became a global success, reaching #1 in several countries, including the United Kingdom, where it stayed at the top of the singles chart for three weeks. In the United States, the song peaked at #24 in April 1989. The song was also highly popular in the early 1990s and was featured on many pop music compilations.
In 1994, the song was licensed to Virgin Records for the best-selling new-age music compilation album Pure Moods, and in 1998 a special-edition 10th anniversary remix single was released. Part of its name is derived from Orinoco Studios (now Miloco Studios), where it was recorded, and its pizzicato chords (generated by altering the Roland D-50synthesizer's "Pizzagogo" patch) is highly recognizable as a new age sound.
Signed to WEA by Rob Dickins, who served as executive producer of Watermark, "Orinoco Flow" was inspired by the Venezuelan/Colombian river, and it paid homage to Dickins in the line "with Rob Dickins at the wheel."
The song was played in the first season of Cougar Town.
YouTuber Seananners references the "Sail Away" lyrics on occasion, notably while playing Gang Beasts, and is partial to the Pure Moods card in Cards Against Humanity due to this song being on that album.
Australian television show Please Like Me features this song in the opening scene of the first episode of its fourth season.
In The Last Man on Earth episode "When the Going Gets Tough", Phil Miller sings the song to Erica as she prepares to give birth to her child.
In the Brooklyn Nine-Nine episode "Crime and Punishment", Jake Peralta mentioned Enya as one of his favorite musical artists. Later on, "Orinoco Flow" plays as he walks, in slow-motion, into a courtroom.