Juanes' joy-filled love song, "Me Enamora," won record of the year, song of the year and best short form music video. He also took trophies for the year's best album, and best male pop vocal album for "La Vida ... Es Un Ratico."
After taking the night's top honor and final trophy, Juanes spoke to the country's Latinos: "You have chosen the right president. Congratulations. It is time to change" -- the last line being the title of his latest song.
The awards bring his total Latin Grammy wins to 17, breaking Alejandro Sanz's mark of 14.
"This is incredible. A million thanks, truly," Juanes said, after the song of the year win. "I have to thank my father, who is in heaven, God, my children. Since I was very young, my family taught me to listen to Latin-American music ... They have all been an influence."
The Medellin-born musician, who has become a voice for social causes, also opened the show's live broadcast with an emotional duet with soul singer John Legend. Backed by a chorus, Juanes and Legend performed "If You Are Out There," a new collaboration that's scheduled to be released next week.
Puerto Rican singer Kany Garcia, a nominee in three categories, walked away with two Latin Grammys, winning best new artist honors and best female pop vocal album for "Cualquier Dia."
Mexican alternative rock group Cafe Tacuba, which led all nominees with six, picked up awards for rock song of the year for "Esta Vez" and alternative song of the year for "Volver a Comenzar."
Latin pop diva Gloria Estefan, who was honored with the 2008 Latin Recording Academy Person of the Year award Wednesday night, also scooped up awards for best traditional tropical album for "90 millas" and best tropical song.
"The only thing left for me to do is to sing in a free Cuba," said Estefan, who is the first woman to receive the person of the year honors.
In pre-show awards, Mexican singer-songwriter Julieta Venegas picked up two Latin Grammys for best long form video and best alternative music album.
This year marked the Houston debut of the awards show, now in its ninth year. The Latin Grammys gives out awards in 49 categories from ranchera to rock en espanol.
The show's lineup of performers reflected the theme of musical diversity and fusion, starting with the opening duet and bursting to life in a rousing accordion jam featuring performers from Colombian vallenato, Argentine tango, Mexican norteno and Tejano genres, and showcasing Julieta Venegas' pop hit "El Presente."
Another of the night's highlights was a vibrant rendition of Gloria Estefan's hits, "Mi Tierra" and "Oye Mi Canto," which featured musical legends Jose Feliciano and Carlos Santana. Feliciano also garnered a Latin Grammy -- his first -- for best contemporary tropical album.
"Winning this award is a source of pride for me, and also for Puerto Rico," said Feliciano, who noted that his birthplace had helped form his musical style.
During the show, a video package highlighted the iconic images and multicultural mix of Houston, the country's fourth largest city. Oil rigs, glass-walled skyscrapers and Tex-Mex food painted a quick portrait of the sprawling metropolis.
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