Pendatchanska was born in Sofia, Bulgaria into a family of renowned Bulgarian musicians. Her grandfather Sasha Popov was a violinist and conductor and the founder of the Sofia Philharmonic Orchestra. Her mother Valerie Popova was an internationally acclaimed soprano who sung regularly at La Scala in Milan from 1983 to 1986. She studied piano from early childhood and graduated from Bulgaria's National School of Music, where her subjects were piano and singing. Her vocal teacher was her mother, Valerie Popova.
Making her stage debut at age 17 in the role of Violetta in La traviata, she soon won the Antonín Dvořák Competition in Karlovy Vary, was placed second in the International Vocal Competition in Bilbao in 1988, and won UNISA singing competition in Pretoria in 1989.
The soprano's debut outside Bulgaria took place in Bilbao, where she sang the title role in Lucia di Lammermoor. Since 1989 she has sung in many of the most prestigious opera houses around the world, including those in Vienna, Paris, Berlin, New York (at the New York City Opera), Rome, Brussels, Washington, Hamburg, Moscow, Turin, Naples, Santa Fe, Bregenz, Monte Carlo, and Tel Aviv.
Pendatchanska performed the title role of Esclarmonde at Teatro Regio in Turin in November 1992 at the age of 22, at which time she was even younger than that of Sybil Sanderson, who created the infamously difficult role at age 24.
During the 1997–2001 operatic seasons Pendatchanska sang the role of Elisabetta in Roberto Devereux (Turin and Naples), Adina in Adina (Pesaro), Suor Angelica in Suor Angelica (Lucca), Luisa in Luisa Miller (Naples and Berlin), and in Ermione (Santa Fe and New York).