The Main Line is named after the former Erie Railroad Main Line, and is listed in timetables with the Bergen County Line since the Bergen County Line is only distinct from the Main Line between just north of the Glen Rock Station and just before Secaucus Junction. The trip on the Main Line is one mile longer than going via the Bergen County Line, although the Main Line is a faster railroad for express trains with just three grade-crossings on the distinct portion of the route, (which has two tracks) and only 5 between Waldwick and Suffern, making the line close to grade-spereated with just 8 on the entire line. On the distinct portion of the line, one grade-crossing is at the Glen Rock Station, one at 5th Avenue, near Hawthorne, and one in the Meadowlands at Valley Brook Avenue. Bergen County Line trains have to navigate 14 grade-crossings. Travel times on this line are 3 minutes slower (37 versus 34) compared to the Bergen County Line because there is one additional station. This portion of the line was once four tracks but has been reduced to 3 between the junction with the Bergen County Line and Waldwick, and just two between Waldwick and Suffern>

For service, Main Line trains operate to all stations hourly or better throughout the day, except for one two hour gap around 2:00pm on Weekends. On Weekends, along with some rush hour trains, and weekday evening trains service operates along the entire line between Suffern and Hoboken. On Weekdays, particularly in the middle of the day and many rush hour services, Main Line service runs only between Waldwick (a few northbound trains terminate at Ridgewood, none originate) and Hoboken, with passengers wanting to continue north (from non-shared Main Line Station) needing to connect with a Bergen County Line train at Waldwick or Ridgewood.

A few Main Line trains are combined with Metro-North Port Jervis Line trains, with 1 Port Jervis line train on weekdays making all Main Line stops, but no southbound weekday trains. On Weekends the situation is reversed with 4 Hoboken-bound trains from Port Jervis making Main Line stops, but no Port Jervis-bound trains. The express trains that run to and from Port Jervis (generally only stopping at Ramsey-Route 17, a few also stop at Mahwah and/or Waldwick) can operate via the Main Line or the Bergen County line depending upon traffic conditions caused by other trains.

The line is not-electrified and all trains use push-pull Comet Coaches, or MultiLevels (these are never on trains to and from Port Jervis) with a diesel locomotive on the end of the train facing away from Hoboken Terminal.