The Porsche driver, who won last time out in the Misano E-Prix and is now championship points leader courtesy of his pole, steadily increased his margin to Vandoorne over all three sectors around the Monte Carlo circuit.
Reigning champion Jake Dennis could only finish ninth for Andretti ahead of ERT's Dan Ticktum.
The German's 1m29.861s left him 0.433s clear and on pole for Saturday afternoon's 29-lap race.
Wehrlein's greatest threat looked like it would come from Jaguar drivers Nick Cassidy and Mitch Evans, but both made mistakes in their respective semi-final duels which cost them the chance of fighting for pole.
Evans lost out against Wehrlein having cut the Nouvelle Chicane, while a small mistake under acceleration out of Sainte Devote looked like it had cost Vandoorne, as the Belgian dropped nearly two tenths to Cassidy in the opening sector.
But the Kiwi had a moment through the swimming pool section that cost him dearly, as he finished 0.461s behind Vandoorne at the line.
Evans finished more than six tenths clear of Porsche's Antonio Felix da Costa during the quarter-final duels after posting a 1m29.725s, the fastest time at that stage of proceedings.
It was a similar situation for Wehrlein in his quarter-final against Maserati MSG's Maximilian Guenther, as he finished more than half a second clear.
In a DS Penske intra-team battle, Vandoorne had the edge on team-mate Jean-Eric Vergne by just over one tenth, while Cassidy progressed at the expense of Envision's Sebastien Buemi.
Ahead of his Formula E debut later today, Taylor Barnard finished last in the second qualifying group, 1.730s behind the fastest time which was set by Vandoorne – a 1m30.593s.
The 19-year-old Briton is set to become the youngest Formula E starter as he replaces Sam Bird after the McLaren driver broke a bone in his left hand following a crash in FP1.
Cassidy finished second in the group, nearly two tenths behind Vandoorne, as Buemi and Vergne progressed to the duels.
Maserati MSG's Jehan Daruvala missed out by 0.162s as he headed Edoardo Mortara (Mahindra), Sacha Fenestraz (Nissan) and the second McLaren of Jake Hughes.
Reigning champion and joint championship leader Jake Dennis could only finish ninth for Andretti ahead of ERT's Dan Ticktum.
Evans continued his impressive practice form by topping the opening qualifying group by 0.154s from Wehrlein, as Guenther and da Costa completed the top four.
Envision's Robin Frijns failed to progress by just 0.002s as he was followed by Sergio Sette Camara (ERT), Nico Muller (Abt) and Nyck de Vries (Mahindra).
Nissan's Oliver Rowland, who claimed victory at the last Formula E event in Italy, could only finish ninth as Lucas di Grassi (Abt) and Norman Nato (Andretti) completed the order.
| Cla | Driver | Team | Time | Delay |
| 1 | Pascal Wehrlein | Porsche | 1'29.861 | |
| 2 | S.Vandoorne | DS | 1'30.304 | 0.443 |
| 3 | Nick Cassidy | Jaguar | 1'30.772 | 0.911 |
| 4 | Mitch Evans | Jaguar | - | - |
| 5 | Jean-Eric Vergne | DS | 1'30.119 | 0.258 |
| 6 | Sebastien Buemi | Jaguar | 1'30.140 | 0.279 |
| 7 | A.F.da Costa | Porsche | 1'30.341 | 0.480 |
| 8 | Max Guenther | Maserati | 1'30.425 | 0.564 |
| 9 | Robin Frijns | Jaguar | 1'31.070 | 1.209 |
| 10 | Jehan Daruvala | Maserati | 1'31.010 | 1.149 |
| 11 | S.Sette Camara | ERT | 1'31.188 | 1.327 |
| 12 | Edoardo Mortara | Mahindra | 1'31.042 | 1.181 |
| 13 | Nico Müller | Mahindra | 1'31.241 | 1.380 |
| 14 | Sacha Fenestraz | Nissan | 1'31.083 | 1.222 |
| 15 | Nyck de Vries | Mahindra | 1'31.279 | 1.418 |
| 16 | Jake Hughes | Nissan | 1'31.149 | 1.288 |
| 17 | Oliver Rowland | Nissan | 1'31.347 | 1.486 |
| 18 | Jake Dennis | Porsche | 1'31.370 | 1.509 |
| 19 | Lucas di Grassi | Mahindra | 1'31.349 | 1.488 |
| 20 | Dan Ticktum | ERT | 1'31.600 | 1.739 |
| 21 | Norman Nato | Porsche | 1'31.353 | 1.492 |
| 22 | Taylor Barnard | Nissan | 1'32.323 | 2.462 |
