Once spanning from Alaska to southern Mexico, the American lion was a formidable big cat that undoubtedly was an apex predator and keystone species throughout its range.

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It was around 4 feet tall at the shoulder and 5'3"-8'2" long, compared to the average male African lion's stature of 6-6'8" long. It was on average 25% larger than the African lion. Their structure is well known due to the large number of fossils that have been found, with about 80 skeletons being unearthed from the La Brea tar pits alone. Preserved skin remains found with a skeleton as well as cave paintings seemly demonstrate that P. atrox's skin was reddish in color.

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It lived from Alaska, southwestern Canada (Alberta), and Maryland on the East Coast in the north, to the southernmost state of Mexico, Chiapas, and potentially even South America down to Argentina. It never moved into New England or eastern Canada, likely due to the presence of dense boreal forests which it was incompatible with.

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It inhabited the same ecotypes as the living African lion: open grasslands and savannas. For this reason, it avoided competition or cohabitation with the jaguar, which favors forests.

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Likely prey items for the formidable American lion were wild horses, members of the deer family (like whitetail deer, mule deer, and elk), young mammoths, bison (including the American bison), tapirs, mastodons, and camels.

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Part of a direct lineage from modern African lions, the American lion began as a population of cave lions around 340,000 years ago. While its genetics and lineage have long been disputed, with contenders claiming it to be a relative of the lion, jaguar, tiger, or even a separate lineage of Panthera, recent genealogical analyses have shown it to be a direct descendant from Africa. Evidence shows that African lions left Northern Africa via the Middle East and speciated into the Eurasian cave lion, which then migrated across Beringia into Alaska where it became isolated and speciated further into the American lion.

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P. atrox bones have been found in the trash heaps of Paleoindians, the ancestors of today's Native Americans, demonstrating that humans did hunt them and could have been a factor in their extinction.

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Due to this very recent speciation, the American lion shares almost all of its genetics with the extant African lion. While there are no active de-extinction efforts for it, it makes it a potentially prime candidate for de-extinction. The main differences, phenotypically speaking, are the aforementioned size and their red skin. Its behavioral differences are not well known, as some argue that as a direct descendant of the modern lion it likely lived in prides, others argue fossil evidence begs to differ (such as the fact that social animals commonly have entire fossilized families discovered, whereas American lions very rarely have more than one individual found in a single location). This means that genetics controlling behaviors may be harder to engineer.