[6] In September 2016, Vargas defeated former WBA super flyweight champion Alexander Muñoz with a 5th-round TKO.
[9] Vargas established control of the fight early on, using his length and head movement to keep the hometown fighter at bay, while landing short combinations.
[11] Vargas made a second defense against Oscar Negrete in another Miguel Cotto undercard, in this case his farewell bout against Sadam Ali.
The bout was scheduled as to co-main event to the Miguel Cotto and Sadam Ali WBO super welterweight title fight.
[13] On 24 November, Vargas' head trainer Ignacio Beristáin revealed it would be their last fight together, as they agreed to part ways afterwards.
[15] Vargas made his third title defense against the twice-defeated Azat Hovhannisyan on 12 May 2018, at the Turning Stone Resort Casino in Verona, New York.
[18] Vargas made his fourth title defense against the WBC Silver super bantamweight champion Franklin Manzanilla on 9 February 2019 at the Fantasy Springs Casino in Indio, California.
[19] The bout served as the co-main event to the DAZN broadcast card headlined by a junior lightweight title fight between Alberto Machado and Andrew Cancio.
[21] Vargas made his fifth title defense against the one-time WBO bantamweight champion Tomoki Kameda on 13 July 2019 at the Dignity Health Sports Park in Carson, California.
Kameda had earned his right to challenge with a decision victory over Abigail Medina to capture the WBC interim super bantamweight championship.
[25] On 13 August, the WBC declared Vargas their super bantamweight champion-in-recess, as he suffered a broken leg in training which left him unable to defend for the remainder of the year.
[26] During this year, Vargas also departed from Golden Boy Promotions and signed with Premier Boxing Champions.
[34] On March 8, 2024 in Riyadh, Saudi Arabia, Vargas retained his WBC featherweight title via split draw against Nick Ball.
[35][36] On 24 August 2022, Vargas received permission from the WBC to enter into negotiations for a title unification bout with the reigning WBA "Super" featherweight champion Léo Santa Cruz.
[39] Vargas suffered the first loss of his professional career, as Foster won the fight by unanimous decision, with scores of 116–112, 117–111 and 119–109.