Blind began his career in the youth academy of his hometown club, Ajax; the same club where his father Danny made his name as a professional. Blind is a product of the Ajax youth system and, while officially still a B-junior, he became a mainstay in the A-juniors during the 2007–08 season. before earning promotion to the Ajax first-team for the 2008–09 season. He was a midfielder through his journey up the Ajax youth levels, often playing the ‘No. 6’ or ‘third centre-back’ role. He showed good promise as a youngster and was made captain of Jong Ajax in 2007. He signed his first professional contract at the age of 17, tying him to the club until 1 July 2010.

On 7 December 2008, Blind made his debut in the Ajax first-team in the away match against FC Volendam. Blind made an immediate impact when he forced a corner kick through a Volendam defender, from which Jan Vertonghen scored the winning goal for Ajax. On 19 December 2008, he signed a contract extension keeping him with Ajax until 30 June 2013.

On 5 January 2010, he joined Groningen on loan for the remainder of the 2009–10 season, during the winter transfer window. At Groningen, Blind was mainly used as a right-back. He was almost sold to Groningen for €1.5 million by Ajax on a permanent basis but the move did not materialize.

On 23 April 2013, it was announced by Marc Overmars that Ajax and Blind had reached an agreement to extend his contract for three years, binding him to the club until the summer of 2016. On 5 May, Blind contributed to Ajax’s third Dutch Eredivisie title in a row, marking the club’s 32nd national title, helping to defeat Willem II 5–0 at home, and securing the top position on the table just one match day from season’s end. Later that day it was announced that Blind had been declared AFC Ajax Player of the Year for the 2012–13 season, after playing an outstanding fifth year for Ajax, from the starting left-back position.

Having had previous call-ups, Blind made his debut for the Netherlands senior team on 6 February 2013, in the starting left-back position, against Italy in a friendly encounter at the Amsterdam Arena. The match ended in a 1–1 draw, with Blind playing the full 90 minutes.

On 30 August 2014, Manchester United reached an agreement to sign Blind, subject to a medical and agreement of personal terms. The transfer was completed on 1 September 2014, for a fee of £13.8 million.

In June 2014, he was selected in the Netherlands squad for the 2014 FIFA World Cup. He was a starter at left wing-back for the team’s opening match against Spain, assisting goals for Robin van Persie and Arjen Robben, as the Oranje won 5–1. He scored his first goal for the Netherlands in a 3–0 defeat of Brazil in the third-place play-off.

On 16 November, Blind sustained a knee ligament injury in the Netherlands’ UEFA Euro 2016 qualifier against Latvia which kept him out of the Manchester United team for the remainder of 2014. On 11 January 2015, Blind returned to the United team, starting in defence in a 1–0 loss to Southampton at Old Trafford. On 8 February, he scored an injury-time equaliser for United in a 1–1 draw against West Ham.

Although throughout the previous season Blind was used as a defensive midfielder or left-back, Blind started the season as a centre-back, where he played for the majority of the season. On 12 September 2015, he scored his first goal of the season in a 3–1 win against Liverpool at Old Trafford, also being named man of the match for his performance.

On 17 July 2018, both Manchester United and Ajax announced they had agreed a transfer for Blind to return to Ajax for a four-year deal and a fee of €16 million with conditional add-ons. On 16 December 2018, Blind scored his first senior hat-trick, in an 8–0 league win over De Graafschap at home, whilst playing as a centre-back.

He is the son of former Ajax defender and former Netherlands national team manager Danny Blind. His wife gave birth to their son in October 2019.

On 21 December 2019, it was revealed Blind had been diagnosed with Myocarditis, and had been fitted with an Implantable cardioverter-defibrillator.

In August 2020, Blind collapsed during a pre-season friendly and was due for medical exams before returning to training.