Creator Owen Dennis conceived Infinity Train in 2010 as a film, inspired by the unsettling feeling of waking up on a flight from China and seeing passengers silently staring into screens in the dark.

As a teenager Dennis, like protagonist Tulip, made amateur video games including point-and-click adventures and mods for Half-Life 2 and Unreal Tournament 2004; he cites Myst as one of his primary influences since age 13.

Dennis has described Infinity Train as 'Saw for kids,' since each season centers on machinery designed to force passengers to overcome personal issues and appreciate life.

The series' animation was produced using traditional animation methods by Sunmin Image Pictures in Seoul, South Korea.

The 2016 pilot became the most-viewed pilot on Cartoon Network's YouTube channel, garnering a million views in its first month and 5.2 million by July 2020, and a fan petition to greenlight it as a series gathered over 57,000 signatures.

According to Dennis, Infinity Train was originally planned to air on HBO Max from the start, but the service's delayed 2019 launch pushed the first two seasons to air on Cartoon Network instead, with Book 3 becoming the first to actually premiere on HBO Max.

Dennis planned for eight total seasons, with unproduced Books 5 through 8 intended to explore the themes of grief, guilt, revenge, and acceptance respectively, with Book 8 touching on Alzheimer's disease; a full script for a Book 5 film focused on Amelia was written but rejected by Cartoon Network Studios for lacking a 'child entry point.'

After being pulled from HBO Max in August 2022 along with all references removed from Cartoon Network's social media, fans caused the show to trend on Twitter, all four seasons topped iTunes' kids and family sales chart, and its DVDs sold out on major retailers with prices spiking on eBay.