He played in Major League Baseball (MLB) for the Philadelphia Phillies, Minnesota Twins, Pittsburgh Pirates, Baltimore Orioles, and Miami Marlins.

After graduating from McClatchy High School in Sacramento, California, Worley was drafted by the Phillies in 2005, in the 20th round, but decided to go to college instead.

[8] He made his first Major League start that day, pitching in the first game of a doubleheader against the Florida Marlins.

[9] Worley earned his first major league win against the Washington Nationals on September 19 of the same year while pitching in relief.

On April 29, 2011, Worley was called up to the majors to be the team's fifth starter when Joe Blanton was put on the disabled list.

Vance threw his first career complete game on July 26, versus the San Francisco Giants.

By September 8 the Phillies won each of his 14 previous starts, including games where Worley did not receive a decision.

[11] Worley finished third in the NL Rookie of the Year voting, behind winner Craig Kimbrel and Freddie Freeman.

[13] On April 1, 2013, Worley made his first Opening Day start against the Detroit Tigers at Target Field in Minneapolis.

He finished his lone season with the Twins 1–5 with a career-high 7.21 ERA in 10 starts, as in 48.2 innings he gave up 82 hits.

Worley was designated for assignment by the Pirates on July 30 to make room for Joe Blanton, acquired in a trade with the Kansas City Royals.

[12] Worley struggled flipping in between the rotation and the bullpen for Miami, going 2–6 and pitching to a 6.91 ERA in 24 games (12 starts).

On January 9, 2018, Worley signed a minor league deal that included an invite to spring training with the Cincinnati Reds.

[21] On April 3, 2018, Worley exercised the opt-out clause in his contract with the Reds, making him a free agent.

[25] He did not play a game for the team because of the cancellation of the ALPB season due to the COVID-19 pandemic and became a free agent after the year.

On April 26, 2021, Worley signed with the Kane County Cougars of the American Association of Professional Baseball.