Millone, who appeared to be the odd man out before arm injuries to Jarrod Parker and A.J. Griffin, gave up three hits, walked two and struck out two in his third spring start and fourth overall appearance.
The Athletics roughed up Giants right-hander Matt Cain for seven runs on six hits in 2 2-3 innings, including a two-run homer by Luke Montz and a three-run shot by Stephen Vogt. Cain also walked three, struck out three and hit a batter.
The Giants got on the board in the bottom of the sixth on a solo home run by Hunter Pence, his third homer in two days.
Athletics: With the injuries to Parker and Griffin, Millone likely will slide into one of those spots. But he isn't looking at his immediate task any differently than if Parker and Griffin were healthy.
"Even when two guys go down, you still have to go out and compete," said Millone, who was 12-9 in 28 games (26 starts) in 2013. "As a team, we just have to be grateful for our pitching depth."
"This was definitely my best spring outing by far. I was able to go out and establish the strike zone. I worked in the two-seamer (fastball) a lot more and kept the ball on the ground."
Giants: Cain knows he will encounter rough spots along the way, "but you never expect it to go bad like that," he said. "You're going to have those days, and you have to let it go. You think about things that happened, but you're not necessarily going to go back to the drawing board.
"I just never found my rhythm today. I was behind in the count a lot."
Athletics: First baseman Daric Barton (left hamstring) had not played since March 8, but started against the Giants and had a single, three walks, drove in a run and scored a run.
Giants: Manager Bruce Bochy said second baseman Marco Scutaro (back) might be ready to play in a game by early next week. Left fielder Michael Morse continues to be out with a strained calf and center fielder Angel Pagan is listed as day-to-day with back stiffness.