Spanic's career started in 1992 when she joined the Miss Venezuela 1992 contest, representing her home state, Guárico, The contest served as a platform to launch her acting career even though it was won by Milka Chulina[2] it led to appearances in Venezuelan telenovelas such as Morena Clara, where she portrayed the villain Linda Prado.

In 1994, Spanic had her first leading role in the telenovela Como Tu Ninguna, which aired for two years and became one of the largest novelas of the country and had an enormous success, including internationally.

After playing Amaranta in Todo por tu Amor (1997), Spanic moved to Mexico, where she acted in La usurpadora (1998), portraying twins Paola and Paulina, which came to worldwide success when the novela was transmitted to more than 125 countries around the world and became one of the most popular telenovelas in the Spanish-speaking world.

La Usurpadora was the first novela to win more than 20 points in the grid of the TV American audience.

As of 2011, Spanic is signed to TV Azteca, and has worked in Emperatriz (2011), La otra cara del alma (2012) and Siempre tuya Acapulco (2014).