Isak missed Newcastle’s last Premier League game against Liverpool and had to be replaced late on in the FA Cup defeat to Brighton. But he came through last week’s training OK and is fit enough to start at the London Stadium, where Howe has made three changes.
Nick Pope replaces Martin Dubravka in goal. Bruno Guimaraes is restored to the side after being rested in the cup with Lewis Miley dropping out. And Harvey Barnes starts on the left in the absence of the suspended Anthony Gordon.
Tino Livramento again plays at left-back, with Lewis Hall ruled out for the rest of the season with a foot injury.
Seventeen-year-old striker Sean Neave is among the substitutes.
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NEWCASTLE: Pope, Trippier, Schar, Burn, Livramento; Tonali, Bruno, Joelinton; Murphy, Barnes, Isak
SUBS: Dubravka, Wilson, Targett, Krafth, Osula, Willock, Longstaff, Miley, Neave
WEST HAM: Areola, Wan-Bissaka, Todibo, Kilman, Cresswell, Scarles, Alvarez, Soucek, Ward-Prowse, Bowen, Kudus
SUBS: Fabianski, Emerson, Mavropanos, Rodríguez, Soler, Paqueta,, Luis Guilherme, Ings, Ferguson