In an emotional dedication to her, Fallon explained all of last week's tapings had been cancelled so he could be with his family following the devastating loss.
The comedian-turned-host started the show by saying, "She was the best audience; she was the one I was always trying to make laugh and she was such a fan of the show, and everything I did."
Holding back tears, he recalled a treasured childhood memory with his mother.
"When we were little, my mom would walk us to the store - me and my sister, and we would hold hands. She would squeeze my hand three times and say, 'I love you.' And I would squeeze back, 'I love you, too.' Last week, I was in the hospital and I grabbed her hand and I squeezed I love you and I just knew we were in trouble, you know?" noted Fallon.
Fallon also thanked the fans for all the support that his family received over the past week.
"I feel so grateful to be able to do this every single night and I'm very appreciative of all the support from all of you that my family has received over the past week. We're going to continue to work really hard to bring light and laughter into the world."
The host concluded by saying, "Thank you for watching, thank you for helping me and my family recover from this loss, Mom I will never stop trying to make you laugh. I love you."