In 1996, Vega starred as young Jo Harding in Twister. She guest-starred in numerous television shows and films, including ER, Follow the Stars Home, Ghost Whisperer, and The Bernie Mac Show. She became known worldwide in 2001 for her role as "Carmen Cortez" in Spy Kids. The first Spy Kids film was a huge success, and subsequently two sequels, Spy Kids 2: The Island of Lost Dreams and Spy Kids 3-D: Game Over were filmed. During the shooting of the three films, she performed most of her own Stunts. In 2011, Vega appeared in the sequel, Spy Kids: All the Time in the World as a grown Carmen Cortez.

In 2003, she was named one of that year's hottest teen celebrities in the July 2003 issue Vanity Fair. In 2004, Vega finished filming two films: Sleepover and State's Evidence. Then the following year she starred in the Lifetime television film entitled Odd Girl Out as a victim of cyber-bullying. She also filmed for another made-for-TV movie, Walkout. In June 2006, she finished filming Remember the Daze, which was released in limited theaters on April 2007. She also finished filming Repo! The Genetic Opera, which was released in 2008. Vega was confirmed as the lead role in Helix, written and directed by Aram Rappaport, which began filming in Chicago in March 2008. Vega was originally cast in the 2009 Robert Rodriguez film Shorts, however, due to her being in Australia for the filming of Broken Hill, she had to be recast. She was replaced by Kat Dennings. She appeared on Broadway in Hairspray, as Penny. In 2009, she played Ruby Gallagher on the ABC Family television sitcom Ruby & the Rockits, which also starred Patrick and David Cassidy.

She recorded three songs for the soundtracks while playing Carmen Cortez in the Spy Kids films. She released her debut single, "Isle of Dreams", to coincide with the release of the second film. She also released "Game Over", for the third film. Another song, "Heart Drive" featuring Bobby Edner, was also recorded for Spy Kids 3. She also has recorded songs for the movie Repo! The Genetic Opera, released in 2008.

Vega sang the song "Christmas is the Time to Say 'I Love You'" in the ABC Family film Santa Baby 2: Christmas Maybe. The track appears on the compilation album Songs to Celebrate 25 Days of Christmas, which was released on November 3, 2009 by Walt Disney Records. The music video for the song premiered during the ABC Family's 25 Days of Christmas programming block in 2009.

Vega married film Producer Sean Covel on October 10, 2010, in a ceremony held in his hometown of Lead, South Dakota. and was walked down the aisle by Robert Rodriguez. In July 2012, Vega announced on Twitter that she had divorced Covel.

Vega played Wick in the 2012 film The Devil's Carnival, a film from Director Darren Lynn Bousman and Screenwriter Terrance Zdunich, who previously worked with Vega in Repo! The Genetic Opera. Throughout 2012, Vega starred in the independent thriller, 2br/1ba, directed by Rob Margolies and co-stars with Spencer Grammer and Kathryn Morris. Vega also starred in the Lifetime Channel movie The Pregnancy Project and her animated film The Clockwork Girl was completed. Vega's film The Mine which was filmed in 2010 got a limited release/screening. Vega also voiced Christina in the animated series Unsupervised and had a guest role on Royal Pains. Vega played the young heroine in Aerosmith's music video "Legendary Child".

Throughout 2013 and 2014, Vega appeared in the films 23 Blast, Machete Kills, Bounty Killer, Wicked Blood, The Remaining, and The Hunters. She also had a role on the Big Time Rush series finale "Big Time Dreams", playing herself. In 2015, Alexa appeared in Do You Believe? (film) as Lacey, who was a young woman who was on her own. In this movie, Lacey feels lonely with no real male figure in her life, because her Father would not spend time with her.

In August 2013, Vega became engaged to actor and singer Carlos Pena Jr. The couple married on January 4, 2014, in Puerto Vallarta, Mexico. The couple share a YouTube channel, LexLovesLos. Their son Ocean King PenaVega was born December 7, 2016.

On August 27, 2015, Vega was announced as one of the celebrities who will compete on the 21st season of Dancing with the Stars. Her husband, Carlos PenaVega was also announced as one of the contestants who will compete against her on the show. She was paired with professional Dancer Mark Ballas. On November 9, PenaVega and Ballas were eliminated and finished the competition in 6th place.