At Island Avenue (MP 2.7), where the Mon Line departs to the southwest, at a wye, while the main line continues southeastward, still with four tracks and speed limit 50-40, past North Avenue, crossovers at CP Penn (MP 1.8), where trains taking the southeast leg of the wye at Island Avenue can gain the correct track, as the Conemaugh Line tracks split off on the east side (but don't yet turn away), the main line tracks reduce to two and the speed limit drops to 20 mph. The line turns east-northeast at the confluence of the Allegheny and Monongahela Rivers (which form the Ohio River in downtown Pittsburgh), passing the new football and baseball stadiums, to Federal Street (MP 0.9), where it turns south-southeast (while the Conemaugh Line continues northeast), and crosses the Alleghany River, turning east on the south side of the river, past the crossovers at CP West Pitt (MP 0.0/353.3), where a 2,250 ft. siding starts, beneath a road bridge overhead and into the Pittsburgh station (MP 353.1). In Pittsburgh, Amtrak trains use the former Pennsylvania Railroad station, the remaining part of which has a north side platform, an island platform and a south side through platform, serving four tracks, with two bay platforms on the east side of the station. The current depot is Amtrak-built, in a corner of the former PRR depot, now used for other purposes. There are umbrella sheds on the platforms west of the end of the overall roof, adjacent to the depot building. The erstwhile PRR Panhandle line once ran where the busway is now, with platforms on that side of the bays and the depot building, descending into the tunnel now used by the light rail line to pass beneath downtown, and then cross the Monongahela River on the Panhandle Bridge..
The line departs the station in a northeasterly direction, with the busway that occupies former trackbed along the southeast side of the line alongside, beneath a five-bridge freeway complex, with umbrella sheds east of it, with speed limit 15 mph past position color-light (in July, 2006) signals and a grade crossing to crossovers at CP Pitt (MP 352.5), where the siding ends, and 30 mph past a road bridge high overhead and crossovers at CP East Pitt (MP 352.2), where the line along the south bank of the Alleghany departs on the northwest side, and turns southeast, with a road bridge overhead, to the crossovers at CP Bloom (MP 351.6), where the connecting track to the former B&O line (used by Amtrak's Capitol Limited) departs on the northeast side of the line.