Upon leaving Schuylkill County, Wiconisco Creek enters Williams Township, Dauphin County. In this township, the creek continues in a westward direction, crossing U.S. Route 209 and passing Williamstown. Further on, the creek enters Wiconisco Township, where it passes by the community of Lykens. Here, it receives the tributary Bear Creek and then the tributary Rattling Creek. Wiconisco Creek then leaves Wiconisco Township and enters Washington Township, where it picks up the tributaries Big Run and Canoe Gap Run. The creek then reaches the end of its valley and turns abruptly north, crossing U.S. Route 209 again. It briefly enters Lykens Township before starting to meander southwest back into Washington Township. Here, the creek crosses Pennsylvania Route 225 and continues meandering in the same direction. It crosses U.S. Route 209 again and enters Upper Paxton Township, where it begins to meander parallel to Berry Mountain. After a while, the creek stops meandering, but continues west, receiving the tributary Little Wiconisco Creek. The creek then reaches its confluence with the Susquehanna River between Lenkerville and Millersburg.