Blind made his professional football debut on 29 August 1979 with Sparta. He stayed under contract with Sparta for seven seasons. In July 1986 he transferred to Ajax, attracted there by manager Johan Cruijff. However, Blind's signing was much to the chagrin of Ajax superstar Marco van Basten, who was upset that his manager had brought in a relatively unknown, defensive player from a fairly small club like Sparta, instead of splashing out on a big-money, big-name transfer. With Ajax he amassed an amazing trophy list, winning all three European trophies (UEFA Cup Winners' Cup in 1987, the UEFA Cup in 1992 and the UEFA Champions League in 1995). He secured the Intercontinental Cup, in 1995 against Brazil'sGrêmio, by scoring the winning penalty in the penalty shoot-out.
He was again a penalty hero when he converted twice against Real Zaragoza in the European Super Cup Final of 1995, which Ajax won 5–1 over the two legs. The two penalties Blind converted were in the 65th and 69th minutes of the second leg.
Blind was known for being a solid, dependable defender and a leader on the field. However, he was also a technically gifted and cultured player who could pass and strike the ball well for a non-attacking player. Whilst famous for being a centre back, Blind started his career as a right full-back.
Blind gained 42 caps for the Netherlands over a 10 year period, scoring once against Greece in a UEFA Euro 1992 qualifier. He made his debut in 1986 against Scotland but was not capped at all in 1987 or 1988, an absence which meant he missed being a part of the triumphant UEFA Euro 1988 side. He did however appear at the 1990 and 1994 World Cups and the 1992 and 1996 European Championships, after the latter of which he retired.
In 2007–08, he became football director at his old club, Sparta. On 15 May 2008 he returned to Ajax, to become the new football director in Amsterdam but switched roles when Martin Jol joined the club to assistant-trainer. Moving to the position of technical director for Ajax at the beginning of the 2011–12 season, on 9 February 2012, it was announced that Blind would retire from his duties as Technical Director at Ajax, concluding a heated dispute surrounding the club's board of directors.
On 1 July 2015, he was named Guus Hiddink successor as a coach of the Netherlands national team.