It begins at Seri Kembangan, near the state/territory boundary between Selangor and Kuala Lumpur, and travels southwards to end at Pandan-Tebrau in Johor.

This section is a six-lane carriageway and serves the southwestern part of Klang Valley, passing by a few major towns.

The expressway connect to Universiti Putra Malaysia via UPM Interchange, which also provide connection to nearby other suburban towns like Seri Kembangan via Besraya and Putrajaya via SKVE as well as Universiti Tenaga Nasional (UNITEN) nearby.

The interchange to ELITE E6 lies in the northern part of Nilai, near the Selangor–Negeri Sembilan border, enabling motorists from the south to Shah Alam and Klang while bypassing Kuala Lumpur.

The expressway later continues to cross on Recron factory, quarries and estates and also the northernmost rest area of the route which is Seremban R&R.

Malacca-Negeri Sembilan border is situated a few kilometers before Simpang Ampat Interchange, and as the exit provides access to Simpang Ampat and Tampin nearby, it also being the last serving close connection to Federal Route 1 before both started to distance between them, with FT1 goes southeast, and E1 goes southwest into Malacca and run parallel, but distant with Lebuh AMJ FT19.

Ayer Keroh is the only interchange that links close to the state's central areas, with a few kilometres north lies the only overhead restaurant of E2 which shares the same name.

As it also passes through Mount Maokil and surrounding hilly areas, a climbing lane is established on the section.

This 47-kilometre stretch passes Mount Maokil and the plains of Seri Medan and Sungai Sarang Buaya.

[3][4] The toll rate for the ticket system for passenger cars excluding taxis as of 2011 is 13.6 sen per kilometre.

Calculated below is maximum rate between Skudai and Sungai Besi, the furthest ends of this section closed system.

They provide free first responder services including small fixes for broken down vehicles, towing and also act as traffic police when there is an incident.

[1] PLUS also provides traffic information to commuters through variable-message signs located on some sections of the expressway, and on Twitter @plustrafik in Malay.

Every rest area and layby includes, as a bare minimum, car parks and public toilets.

Depending on location, laybys can also include petrol stations, a surau, and rarely, food courts, independently operated restaurants and automated teller machines.

Several infrastructures in the Johor state portion of the expressway were constructed by Konsorsium Citra Kontraktor Nusantara, a group of six Indonesian firms and Maha Bina Sdn Bhd of Malaysia.

The Ayer Keroh Interchange had two-lane carriageways until 2009, when it was widened to three and four lanes, ending at Sungai Besi commencing again at E37 Kuala Lumpur–Seremban Expressway.

In July 2010, the operator, PLUS Expressways Berhad, announced that the government had awarded contracts to build a fourth lane on a stretch from Nilai (North) to Seremban.