Joe Bell was on his way to give a talk about bullying and homophobia when he was run over and killed.
Bell's gay teenage son Jadin had committed suicide earlier in the year and he was walking across America to raise awarenes about gay rights.
Bell was hit by a truck on Wednesday evening local time as he walked along the shoulder of a highway in Colorado.
Police believe the driver of the truck, Kenneth Raven, may have fallen asleep at the wheel.
Jadin, 15, died in February after hanging himself in a schoolyard. He had reported being bullied but he didn't leave a suicide note.
Bell began his inspiring cross-country walk in April and planned to finish on the Delaware coast.
He had been on his way to give a talk to a youth group in Hugo, Colorado.
Just before his death, he had posted on Facebook a photo of a road sign with the caption: "Making headway, one step at a time."
The organiser of Bell's Facebook page, Joe's Walk for Change, posted soon afterwards:
"I am very sad to have to announce that our friend Joe Bell was hit and struck by a semi while on his walk last night. Thank you so much for all of your continued support, he loved everyone he came into contact with, and was so appreciative of all of your support. I will update with info as it becomes available. He will continue his journey now with Jadin. Please keep his family in your prayers and thoughts. Ann."
Raven has been charged with careless driving resulting in death.