Big Wapwallopen Creek begins in Crystal Lake in Bear Creek Township. It flows west for several tenths of a mile and enters Fairview Township. The creek turns west-southwest for approximately a mile, passing
Arbutus Peak to the south and crossing
Pennsylvania Route 437. It then turns west-northwest for several tenths of a mile before turning southwest and then west, crossing
Pennsylvania Route 309. It passes through Pole Bridge Swamp and begins flowing along the border between Rice Township and Wright Township. Over the next couple of miles, the creek gradually turns south-southwest, still following the township line. It then passes through Hickory Swale and receives Bow Creek, its first named tributary, from the
left. It turns southwest for several tenths of a mile before turning south and then southwest. It then turns west for more than a mile before turning southwest for a few miles, receiving the tributary Watering Run from the left before entering Dorrance Township and crossing
Interstate 81. The creek then turns south for a few tenths of a mile before turning west and then southwest for a few miles, passing Feys Grove. It eventually turns west-southwest and enters Hollenback Township. After a few miles, the creek turns south for a short distance and receives Balliet Run, its last named tributary, from the left. It then turns west-northwest for more than a mile before turning south. At this point, the creek turns west again and enters a
gorge. After several tenths of a mile, it turns north again, still flowing through the gorge and crossing the border between Hollenback Township and Nescopeck Township several times. The creek then turns west-northwest and begins flowing along the border between Nescopeck Township and Conyngham Township. After approximately a mile, it leaves the gorge and crosses
Pennsylvania Route 239. It then reaches its confluence with the Susquehanna River just southwest of
Wapwallopen.
Tributaries Big Wapwallopen Creek has three named tributaries: Balliet Run, Watering Run, and Bow Creek. The creek also has numerous unnamed tributaries. Balliet Run joins Big Wapwallopen Creek upstream of its mouth. Its watershed has an area of . Watering Run joins Big Wapwallopen Creek upstream of its mouth. Its watershed has an area of . Bow Creek joins Big Wapwallopen Creek upstream of its mouth. Its watershed has an area of . Two unnamed tributaries of Big Wapwallopen Creek include "Big Wapwallopen Creek Tributary E" and "Big Wapwallopen Creek Tributary H". Their watersheds have areas of , respectively. ==Hydrology==