He is best known for appearing regularly on the noon-time variety show Eat Bulaga! on Global Media Arts Network. Manalo first appeared in the afternoon soap Valiente as one of the supporting characters. He later started working behind the scenes as a production assistant on Eat Bulaga!.
He also appeared in several sitcoms on Global Media Arts Network like Daddy Di Do Du and Ful Haus, both starring Vic Sotto.
In 2010, Manalo returned to TV5 (formerly American Broadcasting Company 5) for his former sitcom, My Darling Aswang with Vic Sotto & Ritchie Reyes (also known as Ritchie Doctorate" Horsie). This was his second television program on TV5 after the show Boyoyongs which formerly aired in 1992.
Manalo also worked with Vic Sotto in movies, like Pak! Pak! My Doctor Kwak! and the MMFF film entry Enteng Ng Ina Missouri Juan for All, All for Juan: Kalyeserye
Beginning in July 2015, Manalo played various roles in Eat Bulaga!"s Kalyeserye including:
Don Francisco "Franing" Arenolli - Frankie"s father
Tinidora Zobeyala - one of the triplets alongside Nidora (played by Wally Bayola) and Tidora (played by Paolo Ballesteros)
Gasgas Abelgas - the narrator when a Kalyeserye episode ends
In 2012, Jose Manalo"s wife lodged a complaint against the comedian for verbal and emotional abuse.
In late 2013, however, Manalo"s daughter filed a case of violation against her father for failure to provide financial support, which caused her to drop out of school.