Mahoning Creek is considered by the Pennsylvania Department of Environmental Protection to be impaired by siltation.

Mahoning Creek begins in a valley in Madison Township, Columbia County.

It flows south for a short distance before turning west-southwest for several tenths of a mile, exiting Columbia County.

The creek eventually enters a much broader valley and flows away from Pennsylvania Route 642.

After several tenths of a mile, it crosses Interstate 80 and receives Kase Run, its first named tributary, from the left.

The creek then meanders west for several tenths of a mile and then turns southwest, flowing alongside Pennsylvania Route 642 again.

The creek then turns southeast and begins flowing alongside Pennsylvania Route 54 into Mahoning Township and through a water gap in Montour Ridge.

It enters Danville and leaves behind the water gap, turning south-southwest and crossing US Route 11.

After a few tenths of a mile, the creek receives Sechler Run, its last named tributary, from the left, and turns west-northwest.

[1] Mahoning Creek joins the Susquehanna River 136.26 miles (219.29 km) upstream of its mouth.

The tributary Kase Run reaches its confluence with the creek 4.70 miles (7.56 km) upstream of its mouth.

[3] There is significant stormwater flow and sedimentation in Mahoning Creek, as well as agricultural and urban runoff.

[3] A total of 24,960.6159 pounds (11,321.9449 kg) of sediment from stream banks flows through Mahoning Creek daily.

Turf grass contributes 48.9315 pounds (22.1950 kg) of sediment to the creek daily and land classified as "high-intensity development" by the Pennsylvania Department of Environmental Protection contributes 16.1644 pounds (7.3320 kg) per day.

[3] On average, 39.3 inches (100 cm) of precipitation fall in the watershed of Mahoning Creek each year.

[3] The watershed of Mahoning Creek is in the ridge and valley physiographic region's Appalachian Mountain Section.

However, a small portion of the creek's watershed lies in the neighboring Columbia County.

[8] The mouth of the creek is in the United States Geological Survey quadrangle of Riverside.

A tract of 180 acres in Danville, including an area along the creek, was once owned by the Penn family.

Phillip Maus was among the first settlers in Valley Township, Montour County, having settled there in 1769.

A two-span prestressed box beam or girders bridge with a length of 69.9 feet (21.3 m) was constructed over the creek in 1955 and repaired in 1988.

Another prestressed box beam or girders bridge was constructed across the creek in 1994 with a length of 51.8 feet (15.8 m).

In the same year, a prestressed box beam or girders bridge with a length of 79.1 feet (24.1 m) was constructed over the creek.

The association has carried out watershed assessments and water quality measurements of the creek.

[7] Wild trout naturally reproduce in Mahoning Creek from its headwaters downstream to the US Route 11 bridge, a distance of 9.19 miles (14.79 km).

These include scarlet tanagers, black-throated green warblers, belted kingfishers, gray catbirds, black-capped chickadees, eastern wood-peewees, Louisiana waterthrushes, and wood thrushes.

[3] However, the Mahoning Creek floodplain and the nearby slopes are listed as a Locally Significant site on the Montour County Natural Areas Inventory.

These include skunk cabbage, bloodroot, sensitive fern, sedge, wood anemone, woolgrass, and others.

There are also invasive plants such as multiflora rose, Japanese knotweed, and garlic mustard in the area.