On the same day Barnsley confirmed the arrival of centre-back Conor McCarthy, the Tykes opened the scoring at Worksop after eight minutes through Cole. Leya-Iseka's cut-back found Cole on edge of the area to slot home.
The lead was doubled after 28 minutes when Leya Iseka turned goal-scorer as he prodded home from close range after a Clarke Oduor free-kick was spilled by the goalkeeper.
Shortly before half time, Callum Brittain added a fine third as he fired an effort into the top-left corner from 20 yards.
Michael Duff made wholesale changes at the break, giving his younger players a chance to impress.
Barnsley didn't add to their tally in the second half while Worksop got themselves on the scoresheet after converting a penalty early in the second half.