Route of the E59 starts in Prague, Czech Republic, and proceeds southeast along the D1 motorway towards Jihlava, where it leaves the motorway and turns south along the route 38, a regular road comprising at-grade intersections. The route passes near Moravské Budějovice and Znojmo.^[1] It crosses from the Czech Republic to Austria between Chvalovice and Haugsdorf as it switches to Austrian B303 state road, representing another two-lane road with at-grade intersections. North of Guntersdorf, the E59 transfers to the S3 expressway until it reaches Stockerau and the A22 which carries the E59 east to Vienna. Within the city, the E59 turns south once again in Donaustadt, transferring to the A23 taking it to the southern outskirts of the city. There it proceeds further south along the A2 motorway taking the route past Wiener Neustadt to the city of Graz. Graz itself is bypassed by the motorway and the E59 switches there to the A9 motorway marking the final southbound leg of the E59 through Austria until it reaches Spielfeld/Šentilj border crossing to Slovenia.^[2] South of the border crossing the E59 route follows the Slovenian A1 motorway to the south of Maribor where the E59 leaves the A1 route and joins the A4 taking it to Gruškovje/Macelj border crossing to Croatia.^[3] South of the border, the E59 follows Croatian A2 motorway running past Krapina to Zagreb. The E59 terminates at Jankomir interchange of the Zagreb bypass, where southbound E59 traffic defaults to the eastbound A3 motorway.^[4] Originally the E59 extended further south past Zagreb, to Bihać, Bosnia and Herzegovina and Split at the Adriatic Sea coast, however, that segment of the route was subsequently transferred to the European route E71. Nonetheless, the E59 shares segments of the route with a number of other European routes.^[5] A part of the E59 spanning Prague and Vienna corresponds to the Pan-European Corridor IV, and the segment spanning Graz and Zagreb corresponds to the Pan-European Corridor Xa.^[6]

Various sections of the E59 are tolled, using a range of toll collection systems. In Czech Republic, vehicles exceeding 3.5 tonnes (3.4 long tons; 3.9 short tons) using the D1 motorway are charged toll using an electronic toll collection (ETC) system, while other vehicles are required to have a vignette displayed.^[1][7] The same applies to Austrian motorways.^[8] Slovenia has a similar system in place, although vehicles exceeding the 3.5 tonnes (3.4 long tons; 3.9 short tons) weight limit are provided with a number of payment options.^[9] The Croatian A2 is also a tolled motorway, using a ticket system. As of August 2011, the toll charged along the A2 route between various toll plazas at each motorway exit and two mainline toll plazas, varies depending on the length of route travelled and the vehicle classification in Croatia. The toll is payable in either Croatian kuna or euros and by major credit and debit cards. A prepaid toll collection system is also used.^[10]

UNECE was formed in 1947, and their first major act to improve transportation was a joint UN declaration no. 1264, the Declaration on the Construction of Main International Traffic Arteries,^[11] signed in Geneva on September 16, 1950, which defined the first E-road network. This declaration was amended several times before November 15, 1975, when it was replaced by the European Agreement on Main International Traffic Arteries or "AGR", which set up a route numbering system and improved standards for roads in the list. The AGR went through several changes, with the last one, as of 2011, in 2008.^[12] Reorganization of the E-roads network of 1975 and 1983 redefined the E71 designation previously associated with Hanover–Bremen–Bremerhaven road and assigned it to Košice–Budapest–Zagreb route.^[11][13] The same documents assigned the Zagreb–Bihać–Split section to the E59, as the E71 terminated in Zagreb at the time, however, the most recent revision of the E-network truncated the E59 in Zagreb, and transferred its former southern leg to the E71, shortening the E59 considerably.^[12]

• European long-distance paths
• Road transport
• Autobahns of Austria
• Motorways in Croatia
• Highways in the Czech Republic
• Highways in Slovenia

• UN Economic Commission for Europe: Overall Map of E-road Network (2007)