He played three years of college soccer at Seton Hall University in New Jersey under former United States national team coach Manfred Schellscheidt.

Kljestan signed a Generation adidas contract with MLS, and played USL Premier Development League soccer for Orange County Blue Star in 2005.

He improved his performance in his second year as he recorded four goals and provided 13 assists in 25 matches, helping Chivas to a first-place finish in the Western Conference.

After the trial he returned to Chivas and continued his fine form as he made 25 league appearances during the 2009 season and scored 5 goals and provided three assists.

[4] He made his competitive debut and scored his first goal in the same game on July 27, 2010, in a 3–1 win over Welsh club The New Saints in the third qualifying round of the 2010–11 UEFA Champions League.

[5] In his first season in Belgium he appeared in 34 matches across all competitions scoring 3 goals and helped Anderlecht capture the 2010 Belgian Super Cup.

While at Anderlecht, Kljestan was converted from his traditional number 10 role to a holding midfielder; where he partnered with Argentine Lucas Biglia.

He quickly became a fan favorite as supporters began to call him "Mr. USA" and bring US flags to the stadium to show praise for the team's only American player.

[14] On July 1, 2015, he helped the Red Bulls advance in the U.S. Open Cup, scoring one goal and assisting on another in a 4–1 victory over local rival New York Cosmos.

[17] On October 25, 2015, he scored the eventual game-winning goal for New York in 2–1 victory over Chicago Fire, helping Red Bulls clinch the 2015 MLS Supporters' Shield.

[21] During the third Hudson River Derby match of the season; Kljestan converted a penalty and provided two assists en route to a 4–1 victory.

[22] On August 3, Kljestan scored the third goal in a 3–0 victory against Antigua GFC in the Red Bulls' first 2016–17 CONCACAF Champions League group stage match.

On July 19, 2017, Kljestan scored his first league goal of the season and recorded two assists for New York in a 5–1 victory over San Jose Earthquakes.

[30] On March 17, 2024, Kljestan signed with USL League Two club Des Moines Menace ahead of the team's first 2024 U.S. Open Cup match.

Kljestan made his debut for the senior national team under his former club coach Bob Bradley on June 2, 2007, tallying an assist on Benny Feilhaber's winning goal in a 4–1 friendly match victory over China in San Jose.

In August 2016, Kljestan received his first call-up in over two years for the United States' 2018 FIFA World Cup qualifying matches against Saint Vincent and the Grenadines and Trinidad and Tobago.