Smith was ruled out at third base trying to stretch a double to open the inning, after he drilled a ball off the wall in center field. D-backs left fielder Cody Ross started the smooth relay to shortstop Chris Owings, who fired to third baseman Martin Prado for the tag play.
San Diego's Bud Black used his manager's challenge with hopes of getting the call overturned in a game the Padres trailed, 2-0.
The call, which looked very close on the mammoth replay board at Chase Field, eventually was upheld and Smith had to retreat to the dugout. Black has been successful in six of eight challenges this season.
D-backs manager Kirk Gibson also lost a replay challenge.
In the eighth, with Chase Headley at first, D-backs right-hander Brad Ziegler tried to pick him off. The play was close and first baseman Paul Goldschmidt signaled to Gibson to come out and challenge the call.
Gibson immediately asked first-base umpire Eric Cooper for the review.
The ruling was that the call would stand, meaning there was not enough replay evidence to overturn the call.