The song was released on September 1, 2017 accompanied by a music video directed by Kacho López and filmed at a Comprehensive Cancer Center in Puerto Rico.

The clip shows a woman with breast cancer being injected during a chemotherapy process which gives her strength, proceeding to stand up and lip-sync the lyrics while Daddy Yankee performs the track.

[4] "Yo Contra Ti" has been critically well received, garnering Susan G. Komen Puerto Rico and J. Walter Thompson numerous awards for its campaign, as well as five nominations at the 2018 Cannes Lions International Festival of Creativity for the song and music video.

"[10] Amarilis Reyes, executive director of Susan G. Komen Puerto Rico, said that the track represents "the feeling of our survivors and a clear message of our purpose.

[8] Puerto Rican musician and director of the orchestra Ángel "Cucco" Peña stated that "the frontiers that have traditionally separated classical and popular music have disappeared in the 21st century.

[16][8] The single's cover art is composed by a shot from the music video and features cancer patient Jessie Reyes, who is shown smiling after receiving an injection on her chest during a chemotherapy process.

Daddy Yankee stated that the fifty percent of the profits from digital downloads and track streams will be donated to the Susan G. Komen Puerto Rico foundation.

"[21] Daddy Yankee explained that the song's last lines are "very spiritual" by stating that "cancer can take your body but not your identity" and that "even if death comes, it won't steal who you are.

"[22] A music video for the single premiered on August 31, 2017 on Daddy Yankee's official YouTube channel and was directed by Puerto Rican Latin Grammy Award-winner Kacho Lopez Mari.

[24] The clip features breast-cancer-diagnosed women including Carmen Hernández, Yesenia Mercado, Vicky Núñez, Nayda Ortiz, Zulma Rodríguez, Martiza Perea, and Jessie Reyes,[26] whose experiences inspired Daddy Yankee to write the song.

[10] The clip centers around a cancer-diagnosed woman, portrayed by actual cancer patient Jessie Reyes, who ensures that she will fight against the disease instead of giving up her life.

[27] Daddy Yankee is shown in various cameras performing the song alone and then with the Puerto Rico Symphony Orchestra in a room with lights that interweaves between black, white, and red colours.