Donaldson's two-run blast capped a four-run uprising in the third inning that gave the A's a 6-0 lead and broke the game open.
After A's starter Tommy Milone proved ineffective, Pat Neshek (2-1) came in with one out in the fifth and tossed a scoreless inning of relief to earn the decision.
Jerry Blevins, Ryan Cook, Sean Doolittle and Dan Otero combined to blank the Reds the rest of the way.
Cincinnati's Bronson Arroyo (6-6) was lit up for seven runs on seven hits over four full frames.
Derrick Robinson went 4-for-5 with a run scored and Joey Votto socked a solo homer for the Reds.