Chygrynskiy earned his debut in the Ukrainian Premier League in 2004, at the age of 17. In 2005, he was loaned out to Ukrainian club Metalurh Zaporizhzhya, where he experienced continuous top flight football. After a successful stint at Metalurh, Dmytro was brought back to Donetsk. He quickly emerged as a consistent defender and a leading figure, and first experienced Champions League football when coming on as a substitute against FC Barcelona during the 2004–05 UEFA Champions League. The young player cemented a starting position at the team in the 2006–07 season, by the end of which, at the age of 20, he captained Shakhtar in the Ukrainian Cup final against Dynamo Kyiv in the absence of the regular captain, Matuzalém.

After a successful 2005–06 season, Chygrynskiy was called up to the 2006 FIFA World Cup squad by coach Oleg Blokhin, following the injury to Serhiy Fedorov. Shortly before the World Cup, Chygrynskiy was a member of the Ukraine under-21 team, which finished as runners-up in the 2006 UEFA U-21 Championship. Showing impressive form during the championship, he was selected as a member of the team of the tournament by UEFA. Although set to be a part of Ukraine’s World Cup squad, Chygrynskiy suffered an injury during the closing stages of under-21 competition, which forced him out of the entire forthcoming tournament.

On 26 August 2009, after long negotiations between Shakhtar and FC Barcelona, a deal was reached for the transfer of Chygrynskiy. The transfer was valued at around €25 million and included the clause that Chygrynskiy play in the UEFA Super Cup for his former club, coincidentally against Barcelona. On 31 August 2009, Barcelona confirmed that Chygrynskiy had passed a medical and signed for five years. Chygrynskiy was the first Ukrainian player to ever play for Barcelona and was expected to display his ability with the ball at his feet and “aerial presence and strong defensive skills” .

Chygrynskiy made his debut for Barcelona on 12 September 2009 in La Liga against Getafe CF. He played a full 90 minutes on his debut, a 2–0 victory.

On 6 July 2010, the 23-year-old centre back signed a five-year deal to return to his former club Shakhtar Donetsk for a fee of €15 million, making Shakhtar a profit of €10 million. after spending just one season with the Spanish team, playing just 14 times. On 3 November 2010, Chygrynskiy scored a header against Arsenal in the Champions League from a Jádson free-kick via a deflection off Craig Eastmond.

Chygrynskiy left Shakhtar by mutual consent on 2 February 2015.

On 11 June 2016, Chygrynskiy signed a two-year deal with a possible extension for a third with Greek Superleague club AEK Athens. On 26 February 2017 he scored his first goal for the club in a 3–0 home win against AEL. The following 4 February, he scored in a 2–1 away win against champions Olympiacos, his first goal for the 2017–18 season.