Alderweireld began his professional career at Dutch club Ajax, where he won honours including three consecutive Eredivisie titles.

In 2013, he moved to Atlético Madrid, where he won La Liga and reached the UEFA Champions League final in his first season.

A senior Belgium international from 2009 to 2022, Alderweireld earned 127 caps and represented the country at the FIFA World Cup in 2014, 2018 and 2022, and the UEFA European Championship in 2016 and 2020.

He became first-choice centre back along with fellow Belgian Jan Vertonghen following the departure of former captain Thomas Vermaelen to Arsenal.

[14] He assured himself of a place in the Eredivisie giants' history books on 3 November 2011, heading in Ajax's 100th UEFA Champions League goal in the 2–1 Group G defeat by Auxerre.

[15] In the 2010–11 season, he scored a stunning 25-yard strike at the San Siro against Champions League group rivals Milan in a 2–0 away win.

In the 2011–12 season, Alderweireld made significant strides in his ability as a footballer, also forming a formidable partnership in the heart of the Ajax defensive with captain and fellow Belgian Jan Vertonghen.

On 5 August 2012, during the Johan Cruyff Shield encounter against PSV, Alderweireld managed to score for Ajax in the 44th minute, bringing his club back within a goals difference going into halftime 2–1.

It was a match Ajax would lose 4–2, making it the third Johan Cruyff Shield which Alderweireld participated in and finished as runners-up.

Having been drawn into a group with Manchester City, Real Madrid and eventual runners-up Borussia Dortmund during its Champions League campaign, Ajax had entered into the Europa League at the knockout phase having secured third place in their group, but failed to advance, losing in the second leg match in Romania 4–2 on penalty kicks after extra time.

[18][19] He played 12 matches as the club won La Liga; on 11 May, he headed his only goal of the season, an equaliser in a 1–1 home draw with Málaga in the penultimate round of fixtures, ensuring that Atlético remained in the title race.

[24] On 26 December, he scored his first goal for the club, Southampton's third in a 3–1 away win away to Crystal Palace by heading James Ward-Prowse's corner kick.

[26] On 8 July 2015, Alderweireld joined Tottenham Hotspur on a five-year contract which ran until the summer of 2020 at White Hart Lane, despite Southampton threatening legal action over the transfer.

[32] During his first season at Tottenham, Alderweireld has been recognised by commentators as one of the best defenders in the Premier League,[33][34] forming impressive central defensive partnerships with national team colleague Jan Vertonghen[35][36][37] and later the Austrian Kevin Wimmer.

[48] On 7 February 2018, he returned to the starting lineup in the fourth round replay of the FA Cup against Newport County, which Tottenham won 2–0.

[59][60] He made 29 appearances for the side during the 2021–22 season, scoring once in the quarter-final match of their Emir of Qatar Cup-winning campaign, a 4–1 win over Al-Sailiya on 6 March 2022.

Just over a month later, on 4 June, Alderweireld scored a goal in the 94th minute of the final match day to secure a dramatic 2–2 draw against Genk, handing Royal Antwerp their first league title in 66 years.

[63][64] On 30 August 2023, he helped the club secure a spot in the group stage of the UEFA Champions League for the first time ever, following a 3–1 aggregate win over AEK Athens in the play-off round.