I would argue that humor is utilized in a number of ways in this great play.

Firstly, humor is to be found in the forthright nature of many of the characters. An early conversation between Philomena and Pelajia reveals Pelajia's humorously blunt take on life when she tells her sister that since there's nothing to do and no jobs in Wasy, everyone just gets drunk and "screw[s] each other's wives and husbands."

A local trickster named Nanabush adds further to the humor depicted in The Rez Sisters. Depending on the situation, he is known to manifest as various types of birds or as a Bingo Master. He oscillates between comedy and tragedy, bringing both sanity and mayhem to the story at different times.

The characters' fixation with bingo adds another layer of humor into their lives, which are faced with a myriad series issues, such as poverty and cancer. An important moment in the play takes place when the characters learn of a rumor that "The Biggest Bingo In The World" is coming to nearby Toronto.

Further humor is introduced when the ladies set about raising the money to get to Toronto. These jobs are performed in an amusing pantomime sequence, and the hope of that $500,000 jackpot keeps the tone of the play lighthearted.

While tragedy comes to the character's lives in the form of Marie-Adele's death, the tenacious spirit of our main characters remains unbroken.