Townsend - who turned 34 on Thursday - is among four players brought in to start the Magners League clash against Cardiff Blues on Friday night.
Lock Stuart Grimes, prop Ed Kalman and fellow back Bryan Rennie also come in for the bottom club, who will disband at the end of the season.
Steve Jones, Bruce Douglas and Andy Miller drop to the bench while Ben MacDougall falls out of the side that lost 33-9 to Ulster two weeks ago.
Opeta Palepoi moves from lock to flanker while John Dalziel will make his first start at number eight for more than a year.
Garry Law moves in from the wing to fill the outside centre berth with Nick De Luca pulling on the number 11 shirt.
Head coach Steve Bates said: "Things are hotting up at the top of the table and Cardiff are in the thick of it and are nipping at the heels of the Ospreys, who we've got in the last game of the season.
"We competed well for much of the game against Ulster, despite the final scoreline, which shows that we are determined to keep challenging those at the top of the table."