Senior
On 29 September 2011, Rodríguez received his first call-up to the Colombia senior side for a match against Bolivia on 11 October 2011. He was selected as the man of match due to his performance, including the initiation of the goal scored in the last minute by his former Porto teammate Radamel Falcao which gave Colombia a 2–1 win in La Paz. Under new manager José Pékerman, he played a crucial part in setting up both goals in a 2–0 friendly victory over Mexico. He scored his first goal for Colombia against Peru, and Colombia went on to win 1–0 in Lima in Pekerman's first competitive match.
Rodríguez assisted two goals in a row from 1–0 to 3–0 In the World Cup qualifying match against Uruguay that eventually ended 4–0. He scored a stunning volley from a 30-yard free kick against Chile, leveling the game to an eventual 3–1 away victory boosting Colombia to the second place in the qualifying stages. In the match against Paraguay, he set up the plays leading towards both goals in a 2–0 victory. In Colombia's last international friendly of the year, he assisted the sole goal, allowing Colombia to tie with 2014 World Cup hosts Brazil 1–1. Rodríguez played his first match of 2013 in the second half of the CONMEBOL qualifiers against Bolivia, where he gave a man of the match performance in a 5–0 victory. He set up the second goal thanks to a free kick that he took.
Playing against South American leaders Argentina, Rodríguez suffered an injury in the 30th minute forcing him to be substituted. While the injury was not serious, he was rested and therefore missed the game against Peru days later. He made a good comeback when he scored the winning goal in a 1–0 victory over Ecuador during the final stages of the world cup qualifiers. In a tough match against Chile, he drew both penalties that equalized Colombia from a 1–3 to a 3–3. This drew allowed Colombia to return to the World Cup for the first time in 16 years. Days later, he assisted the first goal with a free-kick while setting up the second in a 2–1 away victory over Paraguay.
Rodríguez continued his play-making form by assisting the first goal and setting up the second against Belgium in a 2–0 victory. He was later voted man of the match. A few days later, He was praised once more as the man of the match in a 0–0 draw against the Netherlands. Rodríguez started in Colombia's opening match of 2014 and scored a penalty against Tunisia in a 1–1 draw at Estadio Cornellá-El Prat on 5 March 2014. In the last friendly before the World Cup, he scored yet another penalty against Jordan in a 3–0 victory.
On 2 June 2014, Rodríguez was named in Colombia's 23-man squad for the 2014 FIFA World Cup and assigned the number 10 shirt. In the team's opening match of the tournament, he set up the first two goals, scored a last-minute goal with a low shot to seal a 3–0 victory over Greece and was named man of the match by FIFA. In the second match, he continued his form by scoring with a header and setting up a second goal for Juan Fernando Quintero in a 2–1 victory over Ivory Coast and was once again elected as man of the match. In the final group stage match against Japan, Rodríguez came on as a second-half substitute and assisted two Jackson Martínez goals before scoring the final goal in a 4–1 victory. At the end of the group stage, he was ranked as the best performing player at the tournament by FIFA.
On 28 June, Rodríguez scored both goals to defeat Uruguay 2–0 at the Maracanã in the round of 16, taking Colombia to its first ever World Cup quarter-finals. These goals made him the first player to score in all of his team's opening matches since Ronaldo and Rivaldo in 2002. His volleyed opening goal was described as "one of the greatest goals the World Cup has ever seen" by opposing manager Óscar Tabárez, who also called Rodríguez "the best player in the World Cup". Because of his performance against the Uruguayans, he was named by FIFA as man of the match for the third time in four matches. The volley was later voted as the best goal in the tournament by more than four million people on FIFA's website and won the FIFA Puskás Award for the best goal of the year. In the quarter-final against Brazil, he scored his sixth goal of the tournament, a penalty in Colombia's 2–1 defeat.
A tearful Rodríguez was consoled by Brazil's David Luiz and stated: "He (David) told me I was a good player. The truth is that having so many superstars hug me did make me happy. We have to raise our heads now and thank Colombia for their support. We are sad because we wanted to keep going and set new records. We gave everything to reach the semi-final, but we have to be proud because we played a great side. I'm crying because we gave everything. We're sad but we also have to feel proud because we left our skin out there." Luiz and Rodríguez also exchanged jerseys. Rodríguez received a standing ovation from the home crowd, ending his first World Cup campaign with six goals and two assists in five matches. On 11 July, he was named on the ten-man shortlist for FIFA's Golden Ball award for the tournament's best player. He then won the Golden Boot as the tournament's top goalscorer despite being eliminated in the quarter finals. Due to his performances, he was named in the World Cup All Star XI and was also listed in the Cup's star XI by Castrol's index rating system in FIFA's website. Argentina legend Diego Maradona argued that Rodríguez, rather than Lionel Messi, should have won the tournament's Golden Ball award.
Rodríguez was called up to represent Colombia at the 2015 Copa América in Chile, where his team was eliminated 5–4 on penalties by eventual finalists Argentina on 27 June, following a 0–0 draw. The following summer, Rodríguez joined Colombia's squad for the Copa América Centenario and was named the team's captain. On 3 June, he started in Colombia's opening 2–0 win against tournament hosts the United States, scoring his team's second goal from the penalty spot although he was forced off early due to an injury. It was initially feared that he would be unable to feature in his nation's second group match against Paraguay, but he recovered in time to start the match, setting up Colombia's first goal, and later scoring one himself in a 2–1 win which sealed his team a place in the quarter-finals of the tournament. Colombia would then lose in the semi-finals against eventual and defending champions Chile, before securing a third-place victory against the host nation for Colombia's best result since 2001.
Rodríguez made his first direct contribution towards qualification, scoring a goal in a heated duel against Copa America champions Chile, securing a 1–1 away draw. In early 2016, he provided both a goal and assist in a difficult away match against Bolivia resulting in a 2–3 victory. Days later, he assisted another goal in a 3–1 home victory against Ecuador. In early August, he contributed both a goal and an assist in Colombia's 2–0 victory against Venezuela.
Starting off 2017, Rodríguez scored a late dramatic goal against a defensive Bolivia after missing an earlier penalty. The 1–0 home victory allowed Colombia to move to 4th place within the qualification group. Days later, he scored and provided a goal in an impressive 0–2 victory in Ecuador. For his first friendly of the year, Rodríguez assisted Radamel Falcao's goal from the corner against European giants Spain. The game would end 2–2. Days later against Cameroon, Rodríguez both provided and scored a goal in a dominating 4–0 victory. For the last qualification match of the 2018 World Cup, Rodríguez scored a crucial away goal against South American rival Peru, resulting in a 1–1 draw and granting Colombia the last automatic qualification spot at fourth place. His last contribution of 2017 for Colombia would be an assist against South Korea, which ended 2–1. Colombia's World Cup preparations in 2018 began against World Cup favorites France, where Rodríguez provided two assists towards a comeback of a 2–0 score to a 2–3 victory. This marked the first victory in Colombia's history over France.
On 4 June 2018, Rodríguez was selected in Colombia's 23-man squad for the 2018 FIFA World Cup in Russia. He did not start in the opening game against Japan after a calf injury during training. He came as a substitute in the 59th minute for Juan Quintero. On 24 June 2018, he provided two assists in a 3–0 victory over Poland and was named as the Man of the Match. Rodríguez had to be substituted in the 30th minute in the final match of the group stage against Senegal due to the injury. He played in all three matches during the group phase, but was forced to sit out of Colombia's last 16 match against England. Colombia lost 4–3 on penalties against England and were eliminated from the World Cup. He was unable to score in those three matches.
On 30 May 2019, Rodríguez was included in the 23-man final Colombia squad for the 2019 Copa América. In the quarter-finals of the tournament against defending champions Chile on 28 June, following a 0–0 draw after regulation time, he scored in the resulting penalty shoot-out; however, Colombia were defeated 5–4 and were eliminated from the competition. On 28 May 2021, Rodríguez was ruled out of the squad for the 2021 Copa América due to his lack of conditioning, i.e. for not having the optimal physical level, as he had recently been recovering from injury.
After Colombia's failure to qualify for the 2022 FIFA World Cup, Rodríguez admitted that he was uncertain about his future with the team. "I don't know what's coming regarding the next phases, I don't know if I'm going to be there or not," he told Diario Sport. "What I do know is that it breaks my heart to lose, it bothers me not qualifying and this can't happen again." On 15 June 2024, Rodríguez earned his 100th international cap in a 3–0 friendly win over Bolivia. On 21 June, he was selected in the 26-man squad for the 2024 Copa América. In the quarter-final match against Panama, he scored a penalty and provided two assists in the first half of a 5–0 victory. In the semi-final clash against Uruguay, he provided the assist from a corner kick for Jefferson Lerma's winner in a 1–0 victory to send his national team to the final. This assist was his sixth at the tournament, which allowed Rodríguez to surpass Messi's record for the most assists in a single edition of Copa América.
Rodríguez was selected in Colombia's 26-man squad for the 2026 FIFA World Cup, becoming the eighth Colombian player to appear in three FIFA World Cup tournaments. In Colombia's second group-stage match, he made his 10th World Cup appearance in a 1–0 victory over DR Congo, equaling the record for most World Cup appearances by a Colombian player, previously set by Freddy Rincón and Carlos Valderrama. On 27 June, he made his record-breaking 11th World Cup appearance in a goalless draw with Portugal. He made his 131st international appearance for Colombia in the World Cup Round of 16, surpassing the all-time record previously held by Colombian goalkeeper David Ospina. However, his country's campaign eventually ended after a penalty shootout defeat to Switzerland.
On 15 September 2026, Rodríguez announced his retirement from international football.
