The visitors went close on several occasions during the first period, but a more intense United emerged after the break, and the manic goalscoring spree left the shellshocked Dutch side with no answer.
Ashley Young opened the scoring, before a double from Mason Greenwood, separated by a Juan Mata penalty, killed off any hopes AZ may have had of toppling United's group position.
Ole Gunnar Solskjaer made nine changes to the side that defeated Manchester City in their own backyard last weekend, and just three players – Axel Tuanzebe, James Garner (making his first Old Trafford start) and Greenwood – remained from the starting XI that began matchday five against Astana.