Samardzija (3-6) retired 12 of the first 13 batters he faced, allowing just a third-inning single to Conor Gillaspie. The only other hit he yielded was a ninth-inning single by Alexei Ramirez.
The right-hander issued a pair of walks and struck out eight in the 108-pitch gem, which lifted the Cubs to a victory in the opener of a four-game home-and-home rivalry series.
White Sox starter Jose Quintana (3-2) surrendered four runs on four hits over six full innings, absorbing the loss.
Notable deaths of 2014 [PHOTOS]
Julius Randle breaks leg during NBA debut