It almost immediately crosses Pennsylvania Route 706 and soon afterwards, it leaves Rush Township and Susquehanna County.

The creek continues south for several miles, passing the community of Merryall and crossing Pennsylvania Route 706.

It then turns roughly south-southwest and begins to flow parallel to Pennsylvania Route 706.

In this community, it crosses U.S. Route 6 and shortly afterwards reaches its confluence with the Susquehanna River.

[1] Wyalusing Creek joins the Susquehanna River 253.02 miles (407.20 km) upstream of its mouth.

[2] The rock in the watershed of Wyalusing Creek consists of shale, sandstone, and deposits of glacial drift.

[2] In the early 1900s, the main industries in the watershed of Wyalusing Creek were a foundry, a furniture factory, a planing mill, agriculture, and dairy.

As of the late 20th century, the dairy industry remains active in the watershed of Wyalusing Creek.

[2] It is possible to canoe on a significant portion of Wyalusing Creek during snowmelt or within four to seven days of heavy rain.

Edward Gertler describes the scenery as "good" in his book Keystone Canoeing.