The Italy international is named in Eddie Howe's starting XI for the 17:30 BST kick-off at St. James' Park while fellow new boys Harvey Barnes and Tino Livramento are on the bench.
Tonali will become the 258th player to represent Newcastle in the Premier League.
Nick Pope starts in goal, with Kieran Trippier captaining the side at right-back and Dan Burn in the left full-back position.
Fabian Schär is fit enough to start alongside Sven Botman in central defence while Tonali joins Bruno Guimarães and Joelinton in midfield.
Alexander Isak gets the nod up front, and he'll be supported by Miguel Almirón and Anthony Gordon.
There's a strong set of substitutes for the Magpies, too, with Barnes and Livramento joined by former Villa man Matt Targett, club captain Jamaal Lascelles, the ever-reliable Sean Longstaff and Jacob Murphy, pre-season stand-out Elliot Anderson and last season's leading goalscorer Callum Wilson.
Martin Dúbravka is the back-up goalkeeper.
Follow the game live with our audio commentary or on X at @NUFC.
Newcastle United: Nick Pope, Kieran Trippier (c), Fabian Schär, Sven Botman, Dan Burn, Joelinton, Sandro Tonali, Bruno Guimarães, Miguel Almirón, Anthony Gordon, Alexander Isak
Substitutes: Martin Dúbravka, Tino Livramento, Matt Targett, Jamaal Lascelles, Sean Longstaff, Elliot Anderson, Jacob Murphy, Harvey Barnes, Callum Wilson