The Blues are currently one-point adrift of the Ospreys, who sit fourth in Conference A.
Anscombe will join the Ospreys next season, but John Mulvihill had no hesitation in selecting the New Zealander.
“I have no doubts over Gareth’s commitment. He is the consummate professional and is hugely competitive. He has had a great season here at Cardiff Blues and will want to go out on a high.
Nick Williams returns to captain Cardiff Blues as Mulvihill makes four changes for Saturday’s match.
With his return to fitness, George Earle drops to the bench and Seb Davies reverts to the second-row.
Elsewhere, Aled Summerhill is back to take his place on the wing in the place of Jason Harries.
Tighthead prop, Dillon Lewis, retains the number three jersey as he is set to hit a half century of appearances for his home region.
Head coach Mulvihill said: “It is great to have Nick back to lead the team on Saturday. He is such an important player to our group, who leads by example, galvanises the team and gets us over the gain-line.
“We have had a great couple of weeks of preparation and the boys a highly motivated to claim a fifth derby win of the season, especially after losing at the Liberty Stadium in January.”
“It’s a winner-takes-all, so whoever wins this game will finish fourth in the pool and will probably be the best Welsh region across the calendar year.
“It’s a game of massive significance for us, after tasting Heineken Champions Cup rugby this year, and we want to go back and player there again next year.”
The Ospreys have been boosted by the returns from injury of Wales captain Alun Wyn Jones and winger George North. Neither have played since Wales’ Grand Slam win over Ireland on March 16th. Jones has been struggling with an knee injury while North broke a bone in his hand.
Number 8 James King will make his 200th Ospreys appearance, becoming just the sixth player to reach that landmark for the Region.
Ospreys head coach Allen Clarke said “Our goal for the season has been to achieve Champions Cup qualification, Saturday provides another opportunity to keep that goal alive.
“Over the last number of months we’ve approached it one game at a time aiming to improve on a daily basis and delivering on the pitch. There’s a tremendous buzz in the camp coming off the back of three bonus point wins. Those performances have been forged on the back of a good balance between quality training and enjoyment.”
“We’re under no illusions to the challenge and level of performance required against Cardiff on Saturday. It’s important we focus on our processes, do what we do well and the scoreboard will look after itself.”
Cardiff Blues: 15. Gareth Anscombe; 14. Owen Lane, 13. Rey Lee-Lo, 12. Willis Halaholo, 11. Aled Summerhill; 10. Jarrod Evans, 9. Lloyd Williams; 1. Rhys Gill, 2. Ethan Lewis, 3. Dillon Lewis, 4. Seb Davies, 5. Rory Thornton, 6. Josh Turnbull, 7. Olly Robinson, 8. Nick Williams (capt.)
Ospreys: 15. Dan Evans 14; George North, 13. Cory Allen, 12. Owen Watkin, 11. Hanno Dirksen, 10. Sam Davies, 9. Aled Davies; 1. Nicky Smith 2. Scott Baldwin, 3. Tom Botha, 4. Adam Beard, 5. Alun Wyn Jones, 6. Olly Cracknell, 7. Justin Tipuric (Capt), 8. James KingMore News
Sign up to our mailing list for a weekly digest from the wide world of rugby.Sign Up Now