In Ukraine, the highway runs through northern regions from the Polish border near Krakovets through Lviv, Zhytomyr, Kiev, Poltava, Kharkiv, and Luhansk to the Russian border near Izvaryne.
Route follows {{Highway M (Ukraine)|10}}, {{Highway M (Ukraine)|06}}, {{Highway M (Ukraine)|03}}, and {{Highway M (Ukraine)|04}}. It passes nine regions: Lviv Oblast, Rivne Oblast, Zhytomyr Oblast, Kiev Oblast, Kiev City, Poltava Oblast, Kharkiv Oblast, Donetsk Oblast, and Luhansk Oblast.
| Route E40 | | Lviv Oblast |
| Yavoriv Raion |
| {{Highway M (Ukraine)|10}} {{European route E|40}} |
| Krakovets | }} | Poland}} border ({{small|{{convert|1334|km|mi}}}}) |
| {{Highway P (Ukraine)|40}}}} | near Yavoriv |
| Novoyavorivsk |
| Ryasne-Ruske | vulytsia Tarasa Shevchenka}} | towards Lviv city • Lviv ring road |
| Pustomyty Raion |
| Kholodnovidka | {{Highway M (Ukraine)|11}}}} • Horodotska vulytsia | access to Lviv city |
| {{Highway M (Ukraine)|06}}}} • Stryiska vulytsia | 10}} |
| {{Highway M (Ukraine)|06}} {{European route E|40}} |
| {{Highway H (Ukraine)|09}}}} | near Pasiky-Zubrytski |
| {{Highway M (Ukraine)|09}}}} | near Vynnyky |
| {{Highway H (Ukraine)|17}} • {{Highway M (Ukraine)|06}}}} | near Hamaliivka • (M06 city route) • Lviv ring road |
| Zhovkva Raion |
| Mali Pidlisky | {{Highway H (Ukraine)|17}}}} |
| Kamianka-Buzka Raion |
| Busk Raion |
| Busk | loops north of the city |
| Olesko | loops north of the city |
| Brody Raion |
| {{Highway P (Ukraine)|39}}}} | near Brody |
| Rivne Oblast |
| Radyvyliv Raion |
| Radyvyliv | loops north of the city |
| Dubno Raion |
| {{Highway M (Ukraine)|19}}}} | near Dubno |
| Rivne Raion |
| Velyka Omelyana | Dubenska vulytsia | Rivne south loop |
| {{Highway P (Ukraine)|05}}}} • vulytsia Vyacheslava Chornovola | near Kvasyliv |
| {{Highway P (Ukraine)|05}}}} • Kyivska vulytsia | near Kruhle • Rivne south loop |
| Hoshcha Raion |
| {{Highway P (Ukraine)|77}}}} | near Hoshcha |
| Korets Raion |
| Korets | loops south of the city |
| Zhytomyr Oblast |
| Novohrad-Volynskyi Raion |
| Novohrad-Volynskyi | {{Highway P (Ukraine)|49}}}} | loops north of the city |
| Pulyny Raion |
| Zhytomyr Raion |
| M06 city route | Zhytomyr north loop • near Ivanivka |
| {{Highway M (Ukraine)|21}}}} | near Oliivka |
| M06 city route | Zhytomyr north loop • near Hlybochytsia |
| Korostyshiv Raion |
| Korostyshiv | loops north of the city |
| Radomyshl Raion |
| Brusyliv Raion |
| Kiev Oblast |
| Makariv Raion |
| Kiev-Sviatoshyn Raion |
| Kiev |
| Kyiv ring road • prospekt Peremohy | 06}} |
| Kyiv Ring Road {{European route E|40}} |
| Borshchahivka | {{Highway P (Ukraine)|04}}}} | near Sofiivska Borshchahivka |
| Teremky | {{Highway M (Ukraine)|05}}}} • Kyiv ring road • streets of Kyiv |
| prospekt Akademika Hlushakoho {{European route E|40}} |
| Demiivka | streets of Kyiv |
| Saperno-Slobidska vulytsia {{European route E|40}} |
| Southern Bridge {{European route E|40}} |
| prospect Mykoly Bazhana {{European route E|40}} |
| Kharkivska ploshcha | {{Highway M (Ukraine)|03}}}} • streets of Kyiv | near the Park of Partisans Glory |
| {{Highway M (Ukraine)|03}} {{European route E|40}} |
| Kiev Oblast |
| Boryspil Raion |
| Shchaslyve | {{Highway P (Ukraine)|03}}}} | near Prolisky |
| Boryspil International Airport | access route |
| Boryspil |
| Boryspil | {{Highway H (Ukraine)|08}}}} |
| Boryspil Raion |
| {{Highway P (Ukraine)|03}}}} | near Ivankiv |
| Baryshivka Raion |
| Pereyaslav-Khmelnytskyi Raion |
| Yahotyn Raion |
| Poltava Oblast |
| Pyriatyn Raion |
| {{Highway P (Ukraine)|67}}}} | near Pyriatyn |
| Pyriatyn | {{Highway P (Ukraine)|60}}}} |
| Lubny Raion |
| {{Highway P (Ukraine)|42}}}} | near Lubny |
| Khorol Raion |
| Velyka Bahachka Raion |
| Reshetylivka Raion |
| {{Highway H (Ukraine)|31}}}} | near Reshetylivka |
| Poltava Raion |
| Poltava |
| Poltava | {{Highway M (Ukraine)|22}}}} |
| Poltava Raion |
| {{Highway P (Ukraine)|11}}}} | near Dudnykove |
| Chutove Raion |
| Kharkiv Oblast |
| Kolomak Raion |
| Valky Raion |
| Kharkiv Raion |
| Korotych | {{Highway M (Ukraine)|29}} • {{European route E|101}}}} | near Lyubotyn |
| Kharkiv |
| north route |
| Pisochyn | {{European route E|101}}}} • Khakiv ring road (north/south loop) | near Nova Bavaria |
| {{Highway P (Ukraine)|46}}}} | near Podvirky |
| Lisne | {{Highway M (Ukraine)|20}}}} |
| Horyzont | Khakiv ring road (north/south loop) | near Rohan |
| south route |
| Pisochyn | {{European route E|101}}}} • Khakiv ring road (north/south loop) | near Nova Bavaria |
| Vysokyi | {{Highway M (Ukraine)|18}}}} |
| Kharkiv Airport | streets of Kharkiv |
| Bezliudivka | {{Highway P (Ukraine)|78}}}} |
| Horyzont | Khakiv ring road (north/south loop) | near Rohan |
| Kharkiv Raion |
| Chuhuiv Raion |
| Chuhuiv |
| Chuhuiv Raion |
| Chuhuiv military range | {{Highway P (Ukraine)|07}}}} |
| Balakliia Raion |
| Vesele | {{Highway P (Ukraine)|78}}}} |
| Izyum Raion |
| Izyum |
| Izium | {{Highway P (Ukraine)|79}}}} |
| Izyum Raion |
| Donetsk Oblast |
| Slovyansk Raion |
| Slovyansk |
| Semenivka | {{Highway H (Ukraine)|20}}}} | near Slovyansk |
| Slovyansk Raion |
| Bakhmut Raion |
| Debaltseve |
| Debaltseve | {{Highway M (Ukraine)|04}}}} | 03}} |
| {{Highway M (Ukraine)|04}} {{European route E|40}} |
| Luhansk Oblast |
| Perevalsk Raion |
| Lutuhyne Raion |
| Luhansk |
| Yuvileine | {{Highway H (Ukraine)|21}}}} | near Luhansk |
| Lutuhyne Raion |
| Rozkishne | {{Highway H (Ukraine)|21}}}} | near Luhansk |
| Krasnodon |
| Izvaryne | A|260}} | Russia}} border ({{small|{{convert|1334|km|mi}}}}) |