The song has soared to the top of the charts through an assist by pop celebrity Justin Bieber, who appears on a remix version with a breathy opening verse in English.
"Despacito," which also features the Puerto Rican rapper Daddy Yankee, is a pop track driven by a reggaeton beat. The lyrics to the song, whose title means "slowly," are full of sexual innuendos.
"Despacito" on Monday came in at number one on the Billboard Hot 100 chart of top-selling US singles, the second straight week it has taken the highest spot.
The song cruised to number one on the back of dominance in streaming and digital downloads, although it fared less well in airplay on US radio stations.
Nearly three-quarters of sales or streams of the song were for the remix with Bieber, tracking service Nielsen Music said.
"Despacito" has ruled the US Latin chart for 16 straight weeks and has racked up more than 1.5 billion views on YouTube.
The song is the first mostly Spanish-language track to top the mainstream US chart in 21 years.
In 1996, "Macarena" by the Spanish duo Los del Rio conquered the United States as it set off an international dance sensation, with the song even figuring at the Democratic Party's 1996 convention.
Daddy Yankee, whose real name is Ramon Rodriguez, said that the chorus and pre-chorus of "Despacito" carried "magic, and a melody that everyone could relate to."
"This is definitely not only a big achievement for Luis Fonsi and for me, but it's a big achievement for music in general," he told Billboard magazine.
"We are crossing cultural barriers and unifying the world through music," he said.
Fonsi, who is better known for his ballads than his incursions into reggaeton, recently wrote on Instagram: "Music has no language. Let's keep making history."
"Despacito" has quickly in the past two weeks become a viral sensation online through a variety of video tributes on YouTube.
In one clip, three Italian comedians listen to the song in a car and pretend to hate it before being won over by the rhythm.
The original video, which features Puerto Rican actress and 2006 Miss Universe Zuleyka Rivera, was on Monday the 24th most-watched ever on YouTube, the highest for a 2017 release.
The all-time most-watched video is "Gangnam Style" by Korean dance-pop artist Psy, another rare non-English track to become a major US hit.