Born in Salvador, Bahia, Matheus Jesus joined Ponte Preta's youth setup in 2015, after being released by Flamengo.
[1] Promoted to the former's main squad in January 2016 by manager Eduardo Baptista, he made his senior debut on 5 May by starting in a 1–0 Copa do Brasil away win against Genus.
[7] After featuring regularly in 2017 Campeonato Paulista, which his side finished second, Matheus Jesus was separated from the first team squad in May 2017, due to an "indiscipline problem".
On 7 March 2018, it was announced that Matheus Jesus would join Japanese side Gamba Osaka on loan from Santos for the 2018 season where he would be coached by his compatriot Levir Culpi.
On 9 May 2019, Matheus Jesus agreed to a loan contract with Corinthians until December, with a fixed buyout clause and an arranged permanent deal until 2023.