The 10th-ranked Pole has won three WTA Tour titles this season and is competing to qualify for the season-ending Sony Ericsson Championships.
Radwanska broke Kanepi in the opening game of both sets and stayed in control throughout.
Radwanska, who had a bye in the first round, will next play either fifth-seeded former champion Nadia Petrova or Katarina Srebotnik of Slovenia.
Flavia Pennetta continued her recent run of good results by beating Agnes Szavay of Hungary 6-1, 6-2 in a first-round match.
The seventh-seeded Italian, who reached the final of the Zurich Open last week, dropped only three points on serve in the opening set and broke Szavay on six occasions.
Madrid Internationals Back In Training
Pennetta beats Srebotnik to reach Zurich semis
