After Oakland's 2009 spring training camp, Denorfia was sent to Sacramento where he played 107 games across all three outfield positions. He appeared in only four games for the Major League club in mid-June and was moved off the 40-man roster at the end of the season.
On December 16, 2009, Denorfia signed a minor league contract with the San Diego Padres and received an invitation to spring training. Denorfia started 2010 in the Padres system, playing the outfield for the Triple-A Portland Beavers. He was called up on May 17 to replace the injured Scott Hairston. He pinch hit that same night, hitting a single. Denorfia remained with the big league club for the rest of the season, batting .271 with 9 home runs in 284 at-bats and starting 44 games in center field, 15 in left and 13 in right. On August 5, he hit an unusual inside-the-park home run in Dodger Stadium. The ball chopped off the dirt cut-out in front of the batter's box only four or five feet in front of Denorfia and then bounced out of the reach of the third baseman before being misplayed alongside the tarp down the left field line. SABR investigated the possibility that the play had set the record for least distance travelled through the air for a home run ball.
Denorfia played for Italy in the 2009 World Baseball Classic, starting all three games in center.
Denorfia married his wife Lauren in 2009. His nickname is "Deno", popularized by a fan made tribute video on YouTube titled "Look at Deno", a spoof of the song "Look at me Now".