For many years Lod (then called Lydda) was the main railway hub of mandatory Palestine and later Israel as it sits at the intersection of several major rail lines located in the central part of the country.

Also, before the establishment of the state of Israel, the Coastal Railway did not exist, neither did westbound spurs from the Eastern Railway and therefore all traffic from the north of the country bound for Tel Aviv and Jaffa had to first proceed southwards to Lod, then reroute northwest through the station.

The station's location was changed following World War I, when the British rebuilt the Jaffa–Jerusalem line to standard gauge.

The sprawling site also houses a large rail yard and extensive rolling stock maintenance facilities.

In late 2021, Lod station's electronic signage was upgraded to display information in Arabic, in addition to Hebrew and English.