Isla started his career in the youth system of Universidad Católica, and later moved to Italian club Udinese in 2007, where he made his professional debut. His performances earned him a transfer to defending Serie A Champions Juventus where he won consecutive league titles during his first two seasons with the team. In 2014, he was sent on loan for a season to English side Queens Park Rangers, while he also spent the next season on loan with French club Marseille.