Born in Fray Bentos, Uruguay, Ramírez moved to the capital city Montevideo to join Peñarol when he was sixteen.

Despite being absent from the Torneo Apertura campaign due to international commitments,[5] He scored his first Peñarol goal in a 5–0 win over Atenas on 13 December 2009.

[56] After suffering a leg injury,[57] Ramírez went on to score two more goals later in the season on 2 March 2013, in a 2–1 loss against Queens Park Rangers.

[59] However, on 27 April, Ramírez was sent off for an incident involving West Bromwich Albion's Marc-Antoine Fortuné following an elbow on Shane Long.

Ahead of the 2013–14 season, Ramírez was linked with a move to clubs around Europe, such as Atlético Madrid and Borussia Dortmund for around 15 million euros.

[69] After being sidelined for six weeks, Ramírez made his return to the first team on 22 February 2014, coming on as a substitute in the 63rd minute, in a 3–1 loss against West Ham United.

Although he made one appearance in the 2014–15 season, in a 3–1 win against West Ham United on 30 August 2014,[71] newly appointed manager Ronald Koeman was keen on using him in the first team, due to his playing style, and expressed reluctance to let him leave the club.

[74] Despite this, he made his first appearance for the club in a year, coming on as a substitute in a 6–0 win over Milton Keynes Dons in the second round of the League Cup.

[76] A month later on 25 October 2015, Ramírez made his first league appearance for the club, where he provided an assist for Sadio Mané, in a 1–1 draw against Liverpool.

[84] Ramírez was given a straight red card for kicking Tottenham Hotspur's Jan Vertonghen in Hull's 1–2 home defeat on 23 November.

[85] He scored once in 22 games for the Tigers – equalising in a 3–1 win at Sunderland on 26 December with a 30–yard strike, before assisting James Chester's header via a corner kick.

On 26 January 2016, Ramírez joined Championship side Middlesbrough on loan until the end of the season, when his Southampton contract was due to expire.

[90][91] He made his debut on 9 February in a 1–1 draw at MK Dons, and two weeks later he scored his first Boro goal, giving them the lead in a 3–1 win against Cardiff City at the Riverside Stadium.

[92] On 4 March, he struck both goals in a 2–1 home win over Wolverhampton Wanderers, putting his team on top of the Championship table.

[96] On 7 May, he was part of the Middlesbrough side that won promotion to the Premier League with a man of the match performance in a 1–1 draw with Brighton & Hove Albion, despite sustaining an injury following a challenge by Dale Stephens.

[103][104] After serving a suspension for receiving a yellow card during the match against Bournemouth,[105] Ramírez then scored against his former club, Hull City, in a 1–0 win on 5 December 2016.

[113] Following Middlesbrough's relegation in the Premier League at the end of the 2016–17 season, Ramírez made a total of 26 appearances, scoring twice.

[115] Amid Ramírez's uncertain future, manager Garry Monk called him up in the club's pre-season tour and featured him in the friendly match against Oxford United.

[116] Although Monk praised Ramírez' return,[117] his appearance against Augsburg on 29 July 2017 resulted in boos and jeers from Middlesbrough supporters, leading to accusations from club legend Bernie Slaven in the Teesside Gazette of double standards.

[5] On 8 October 2010, he received his first full cap for Uruguay in a 7–1 friendly win against Indonesia in Jakarta, replacing Diego Pérez at half time.

On 26 July, he scored from a free-kick to equalise as Uruguay won 2–1 against the United Arab Emirates at Old Trafford in their opening game,[130] although they were eventually eliminated at the group stage.

[131] Ramírez started the first group game against world champions Spain,[132] and the third match against Tahiti,[133] as Uruguay eventually came fourth.

Three minutes later he supplied the cross from which Diego Godín scored the only goal of the game, putting Uruguay through to the knock-out stages.