Vargas started his career in the youth teams of Caracas. He was promoted to the first team in 2006. His debut in the Copa Libertadores came on 14 March 2006 against Cienciano. Ronald scored his first goal in the final of the 2006–07 Primera División against Unión Atlético Maracaibo, in a 0–1 victory.

The 2007–08 season established him as a regular player in the starting line-up of Caracas. His first goal of the season came on 21 October 2007 in a league match against El Vigía. He ended the campaign with 29 games and 8 goals. In that season he also made his debut in Copa Venezuela and scored his first goal in Copa Libertadores.

On 14 May 2008, Vargas signed with the Belgian team Club Brugge on a four-year deal. Caracas received €1.5 million, making this the most expensive transfer from a Venezuelan team in history. He made his debut on 29 August in a league match against AFC Tubize, in a 4–1 victory. His debut in the UEFA Cup came on 18 September, in a 2–2 draw against BSC Young Boys, and he scored his first goal in the competition on 27 November in another draw, this time 1–1, against AS Saint-Étienne.

Vargas has played 23 times for the Venezuela national team, scoring 3 goals. His debut came in the 1–0 match against Haití, in February 2008. He scored his first goal in the historic win against Brazil at the Gillete Stadium, in June 2008; his partner Giancarlo Maldonado scored too, and Venezuela won 2–0.

On 9 September 2009, Ronald Vargas scored the last goal in Venezuela’s 3–1 victory over Peru.

In the 2010–11 season Ronald started with top performances, scoring, among other goals, four braces against Westerlo, Charleroi, Zulte-Waregem and Standard Liège. Vargas continued his good form in the start of the second part of the tournament, but on 6 February 2011 he suffered an anterior cruciate ligament injury in a league match against KRC Genk, only eight minutes after the start of the match. He was expected to be out for over six months, missing the chance of playing with his national team in the 2011 Copa América.

Contractual differences between Vargas and Club Brugge emerged in summer 2011, finishing with his transfer to R.S.C. Anderlecht on 29 June 2011. The transfer fee was reported to be €2.5 million. Because of the rivalry between the two clubs mutual transfers aren’t very common. It was the first transfer from Club Brugge to Anderlecht since Aleksandar Ilić in 2000.

On 28 July 2014, Vargas signed a one-year contract with the Super Lig side club Balıkesirspor. On 20 September 2014, he made his debut with the club in a 2–0 home win against Galatasaray and he scored his first goal two months later in a 3–1 home loss against Sivasspor. At the end of the season did not renew his contract with the club.

As AEK Athens officially announced that Vargas had signed a contract with his new team. The 28-year-old forward came to Athens and a few hours later he signed his two-year contract with his new team. On 22 August 2015, he made his debut with the club in a 3–0 home win against Platanias scoring the second goal. On 13 November 2015, AEK’s midfielder suspended for three games after his red card in a Super League game. The Venezuelan was sent off in the last moments of first half against Asteras Tripolis for hitting an opponent.

On 6 January 2016, AEK won against Levadiakos in their first leg Greek Cup tie and are close to qualifying for the last eight of the tournament. Vargas scored a wonderful goal sealing his club victory. On 24 January 2016, thanks to a strike by Venezuelan midfielder, AEK won 1–0 against PAOK and remain at the second Super League position, behind the previous year’s champions Olympiacos. Vargas was impressive in January 2016, scoring four times, and was honored by magazine Diario Goleador as the best Venezuelan footballer of the month. AEK Athens manager Gustavo Poyet used the 29-year-old international mostly as right winger, which helped him scoring more and also creating goals for his teammates.

On 13 February 2016, Vargas scoring after Diego Buonanotte’s missed penalty kick, helping his club to escape with a 1–0 win against the undefeated champions Olympiacos. It was the key player coming as a substitute in the derby whereas referee sent off visitors’ Alberto Botia, Luka Milivojević (for the penalty incident) and home team’s Rodrigo Galo Brito, while Felipe Pardo suffered a strain injury during first half. It was named Man of the match. On 28 February 2016, thanks to a free kick from Vargas, who was also the only scorer against PAOK and Olympiacos, AEK beat rivals Panathinaikos 1–0. Greek Cup’s final against Olympiakos was most likely the last appearance of Vargas in season, as the 29-year-old international has suffered a left adductor strain injury.

On December 2016, the agent of Venezuelan attacking midfielder was in talks with the administration of AEK over his client’s contract extension. The current contract of 30-year-old international expires at the end of 2016–17 season, and his agent wanted to ask technical director of the club Daniel Majstorovic if they are interested in extending it before January 2017 or not. On 22 April 2017, he received an offer for a two-year contract extension, with an annual fee of €300,000. Despite his team’s desire to maintain his services, Vargas will leave the club as he isn’t pleased with either the offer or his team role. After the announcement of his upcoming departure he was heavily linked with Panathinaikos.

In September 2017, Vargas signed for Australian A-League club, Newcastle Jets on a one-year deal as their marquee player for the 2017–18 season. In a Round 3 clash with the Brisbane Roar, Vargas suffered a compound fracture of the leg, ruling him out for a large part of the season, a short time in to his A-League career. Four months later, he returned. He appeared in Newcastle’s Grand Final loss to Melbourne Victory.