Having been included in the squads for five FIFA World Cups (2006, 2010, 2014, 2018, and 2022), Ochoa has gained international recognition for his consistency and big game performances in the competition over multiple iterations.

[12] Guillermo Ochoa made his debut with América during the Clausura 2004 tournament against Monterrey, being only 18 years old when called up by head coach Leo Beenhakker.

[13] Ochoa quickly demonstrated his skill and talent in goal, and the young goalkeeper was thrust into the spotlight to replace injured veteran Adolfo Ríos.

[25] On 4 July 2011, Ochoa signed a three-year contract, with an additional one-year option,[26] with French club Ajaccio, recently promoted to Ligue 1.

After officially announcing his departure, the club bid farewell to Ochoa in an open letter on social media.

[43] Despite having participation with the club during the pre-season, Ochoa had not made any league appearances, with Carlos Kameni being manager Javi Gracia's first-choice goalkeeper.

[44] On 3 December, Ochoa played his first competitive game for Málaga, in a 1–1 Copa del Rey draw against Deportivo de La Coruña.

[45] By early November, media speculation linked Ochoa with a possible January transfer to Liverpool in a £4 million deal.

[46] Despite rumours continuing to flourish and Mexico manager Miguel Herrera expressing displeasure with his first-choice goalkeeper receiving limited playing time, no move had materialized by the end of the January transfer window, with Málaga expressing they were pleased to retain Ochoa, adding the player had been "a professional".

[47] Ochoa was ranked seventh in the International Federation of Football History & Statistics' list of the world's best goalkeepers for 2014.

[51] It was reported in April 2017 that Ochoa was set to be a free agent at the end of the 2016–17 season due to the expiry of his contract with Málaga.

[54][55] On 9 July 2017, it was announced Belgian club Standard Liège had signed Ochoa from Malága on a two-year contract.

[60] Though details of the transfer were undisclosed, it was reported that Ochoa will be the highest-paid Mexican player in the Liga MX, earning US$4.4 million annually.

[66] On 29 August 2020, he wore the captain's armband for the first time since returning to Club América in their 2–1 victory over Atlético San Luis.

[67] Following a 1–0 win against Querétaro on 24 August 2022, Ochoa became the goalkeeper with the most clean sheets in Club América's 105-year history, breaking the previous record of 110 held by Adrián Chávez.

[68] On 23 December 2022, Ochoa signed for Italian Serie A club Salernitana, agreeing a contract until 30 June 2023 with a one-year extension option.

[72] Ochoa was included in the roster to participate at the 2004 Summer Olympics in Athens, Greece,[73] but saw no playing time as the third-choice goalkeeper.

On 14 December 2005, at age 20, Ochoa made his senior national team debut in a friendly match against Hungary, which Mexico won 2–0.

Ochoa was a part of the squad which participated at the 2007 CONCACAF Gold Cup, appearing once in a group stage match against Cuba as Mexico finished runner-up to rivals the United States.

He also played for Mexico at the Copa América that same summer, being praised for his performance in the 2–0 group stage victory over eventual-champions Brazil.

[86] Ochoa made the final 23-man cut for the 2010 World Cup, but was controversially named back-up goalkeeper to veteran Óscar Pérez by coach Javier Aguirre.

[78][83] During the 2011 CONCACAF Gold Cup, Ochoa—along with four other members of the Mexico national team—tested positive for the banned substance Clenbuterol and were withdrawn from the team's tournament squad.

[87] All players were later acquitted by the Mexican Football Federation and the results were blamed on contamination of meat, with the ingestion of clenbuterol considered non-intentional.

[94] On 17 June, in the second group stage match against hosts Brazil, Ochoa made four notable saves,[95][96][97] including one following a powerful header from Neymar that helped secure a 0–0 draw,[98] immediately drawing comparisons to Gordon Banks' famed 1970 World Cup save against Pelé.

[99] Ochoa was named man of the match,[99] earning praise from many, including Brazilian head coach Luiz Felipe Scolari.

[106] In Mexico's third place match against Portugal, Ochoa managed to contribute various crucial saves, additionally stopping Andre Silva's 17th-minute penalty kick attempt.

[108] In Mexico's opener against Germany, Ochoa made a total of nine saves, notably pushing a goal-bound Toni Kroos free-kick onto the crossbar, and ultimately securing a clean sheet in the 1–0 victory.

[114] As Mexico defeated the United States in the final, he was included in the tournament's Best XI[115] along with winning the Golden Glove Award.

[12] During the course of the tournament, Ochoa kept a total of four clean sheets, winning the Golden Glove award and being included in the competition's best eleven.

When the rivals made it past the defense, Ochoa knows how to work inside the box to cover his goal as much as possible by narrowing the angle.