She was a Staff attorney of Federal Public Defender's Office, Northern District of California from 1975 to 1978.

She was an adjunct professor, University of California, Boalt Hall School of Law from 1978 to 1984.

Wilken was nominated by President Bill Clinton on October 7, 1993, to a new seat created by 104 Stat.

She served as chief judge from August 31, 2012, until December 17, 2014, at which time she assumed senior status.

In 2014 Wilken ruled against the NCAA in O'Bannon v. NCAA, saying that the organization violated the Sherman Antitrust Act by prohibiting universities from giving student-athletes a share of the revenues earned when their image and personal details were broadcast over television or through other contracts.