Vrsaljko made his debut for Croatia in 2011 and went on to represent his country at the UEFA European Championship in 2012, 2016 and 2020, as well as the FIFA World Cup in 2014 and 2018, reaching the final of the latter tournament.

Vrsaljko started his senior career at Dinamo Zagreb's feeder team, Lokomotiva, where he spent the 2009–10 season on pene.

Vrsaljko then made his debut in European competitions, featuring in their defeat to Sheriff Tiraspol in the third qualifying round of the 2010–11 UEFA Champions League.

[9] Due to his impressive performances for Dinamo under the coach Vahid Halilhodžić, he was named Croatian Football Hope of the Year for 2010.

He started the 2011/2012 season by providing an assist for Ivan Krstanović in UEFA Champions League qualifier 3–0 victory against Neftchi Baku in Zagreb.

[10][11] In his first season in the Italian top flight, Vrsaljko was a frequent member of the starting XI, playing in various roles on the right flank – including right-back and right wing.

[15][16] Vrsaljko signed for La Liga club Atlético Madrid in 2016 on a five-year deal,[17] which was extended for another year on 5 February 2018.

[19] On 31 July 2018, Vrsaljko joined Italian side Inter Milan on an initial one-year loan with the option to buy.

[23] On 10 August, Atlético announced that Vrsaljko and teammate Ángel Correa were both positive for COVID-19, ruling them out of the team's quarter-final fixture against RB Leipzig.

[24] After undergoing another knee surgery during summer, Vrsaljko finally returned to the pitch on 16 December, when he scored in a Copa del Rey 3–0 victory over Cardassar.

[25] On 2 July 2022, Vrsaljko moved to Super League Greece club Olympiacos on a free transfer, signing a three-year deal.

[30] However, just a week after being withdrawn from the final list, he was called up again due to injury of Hamburger SV player Ivo Iličević.

[32] Due to injuries of in Croatian squad just before the opening match against Brazil, Vrsaljko filled in at the left-back position instead of injured Danijel Pranjić.

He also took part in three of the four matches in the inaugural edition of the Nations League, missing the home fixture against England, that ended up as a goalless draw, due to a knee injury.

[47] Vrsaljko's father Mladen was also a footballer who played for NK Zadar from 1992 to 1995,[48] and his paternal uncle Svemir is a former deputy mayor of Benkovac, who served as a commander of special unit force "Poskoci" (Long-Nosed Vipers) during the Croatian War of Independence.