MacDonald, who signed a one-year, $925,000 contract with the Flames Saturday after being acquired from Detroit in February, backstopped Calgary to its fifth win in six games.
The netminder stopped all 22 shots he faced over the final two periods, when the Flames used tallies from Mikael Backlund and Michael Cammalleri to forge a 3-1 lead.
Mark Cundari netted his first NHL goal and Jiri Hudler added an empty-netter for Calgary, which has been eliminated from playoff contention.
Zach Parise scored for the Wild, who came into the contest clinging to three-point lead over the Detroit Red Wings for one of the final Western Conference playoff spots.
Niklas Backstrom made 20 saves for Minnesota, which fell for the fifth time in seven games.