Feliciano, a member of the Fania All Stars, was one of the most recognized salsa singers, with hits including "Una en un millón," ''Mi promesa," and "Contigo aprendi."
The 78-year-old Feliciano was alone in his Jaguar when he hit a light post before dawn in the northern suburb of Cupey. Police officer Jorge Hernandez Pena, who is overseeing investigation of the crash, said in a phone interview that Feliciano was not wearing his seatbelt.
He said it is unclear what led to the crash, adding that officials did not find any drugs or alcohol in the car.
His wife of 56 years, Socorro "Coco" Prieto Leon, told reporters that Feliciano had been at a casino Wednesday night.
"He was the only man in my life," Prieto said as she cried. "I thank everyone for the love they had for him."
Puerto Rico Gov. Alejandro Garcia Padilla declared three days of mourning, saying, "Today, Puerto Rico lost one of its greatest voices."
U.S. Rep. Nydia Velazquez issued a statement calling Feliciano a treasure to Puerto Ricans and to many New Yorkers.
"His music embodied the rhythm of Puerto Ricans living in New York City and his lyrics helped tell our collective story," she said.
The music community also mourned.
"Cheo, my friend, I'm in so much pain. You will always be one of my heroes," tweeted New York salsa musician Willie Colon.
Cheo Feliciano was born in the southern coastal city of Ponce and formed his first band when he was about 8, playing instruments made from cans, according to a February 2000 interview he gave online music site descarga.com.
Feliciano's father struggled to find work as a carpenter, and his family moved to New York when Feliciano was a teenager.
Shortly after arriving, Feliciano joined a local band as a percussionist and became friends with music giants including Tito Puente.
On Oct. 5, 1957, Feliciano married Prieto, a Puerto Rican dancer, and that night, gave his first concert as a singer with the Joe Cuba band.
A decade later, he left the band and then collaborated with Eddie Palmieri on his album, "Champagne," but succumbed to heroin addiction shortly afterward and withdrew from the spotlight for nearly three years.
He returned to his native Puerto Rico for rehab, became a staunch anti-drug spokesman and joined the Fania All Stars in 1972. That same year, he released "Cheo," a solo album that is considered one of his best.
In the mid-1980s, he launched his own production company called Coche Records and produced five albums.
To celebrate his 50 years as a musician, he performed in New York's Madison Square Garden in 2008, singing alongside Palmieri and others including Papo Lucca and Ismael Miranda.
Feliciano had been hospitalized last year for pneumonia and was fighting cancer.
He is survived by his wife and several children. Prieto said he will be buried in his hometown of Ponce.
Singer and guitarist Jose Feliciano also was among the dozens of musicians lamenting his death. His New York publicist, Judy Katz, noted that some media were incorrectly reporting that the guitarist had died.
Associated Press writers Isaac Garrido and Berenice Bautista in Mexico City contributed to this report.