The reigning F1 world champion clocked a 1m48.984s to finished 0.498 seconds quicker than his title rival, who was fastest in both practice sessions on Friday.
Ferrari proved to be Mercedes’ closest challenger at a gloriously sunny Spa Francorchamps, with Sebastian Vettel third and his team-mate Kimi Raikkonen fourth.
Sergio Perez set the fastest final sector as he ended up fifth, two tenths and three places clear of team-mate Nico Hulkenberg to suggest Force India can aim for the final part of qualifying later on Saturday.
The Red Bull drivers and Toro Rosso’s Max Verstappen, who will start towards the back of the grid because of a 10-place grid penalty for an engine change, completed their soft tyre qualifying-simulations early in the session.
That allowed them to spend the rest of the session to gathering long-run data, making up for the red flag disruptions in Friday’s second practice.
Daniel Ricciardo was sixth quickest, 0.050s ahead of Red Bull team-mate Daniil Kvyat, with Verstappen 13th overall.
The Williams of Valtteri Bottas and Felipe Massa completed the top 10 ahead of Toro Rosso’s Carlos Sainz Jr in 11th and Lotus’s Pastor Maldonado in 12th.
It was a difficult day for McLaren-Honda, whose cars are already destined to stat at the back of the grid following a host of engine penalties.
Fernando Alonso managed just a single installation lap before returning to the garage.
The action started with a an incident involving Manor’s Roberto Merhi, who spun under braking at the Bus Stop before he managed to continue.
Rosberg put Mercedes on top seven minutes into the session, but was soon relegated to second by Nico Hulkenberg, before Ricciardo became the first man to dip into the 1:50s some 10 minutes in.
Raikkonen moved to second place before he went off at Les Fanges, managing to return to the track after a trip through the gravel.
Hamilton went fastest after 15 minutes, the Briton outpacing Ricciardo by 0.045 seconds, still running on the medium tyres.
Ricciardo returned to P1 with his first run on soft tyres, the Red Bull driver setting a new benchmark of 1:49.930.
Teammate Kvyat made it a Red Bull 1-2 on top of the times with a time just half a tenth slower than the Australian.
Rosberg waited until the 47-minute mark to try the softer rubber, and he put it to good use, jumping to the head of the times with a 1:49.482, still over a tenth off his best from Friday.
Hamilton then set the quickest time of the weekend with the soft tyres as he became the first driver to lap in the 1:48s in the Mercedes, outpacing Rosberg by nearly half a second.
| Pos | Driver | Car | Time/Gap | Laps |
|---|---|---|---|---|
| 1 |  Lewis Hamilton |
Mercedes | 1:48.984 | 15 |
| 2 |  Nico Rosberg |
Mercedes | 0.498 | 19 |
| 3 | Sebastian Vettel |
Ferrari | 0.645 | 17 |
| 4 |  Kimi Raikkonen |
Ferrari | 0.880 | 19 |
| 5 |  Sergio Perez |
Force India | 0.882 | 15 |
| 6 |  Daniel Ricciardo |
Red Bull | 0.946 | 20 |
| 7 |  Daniil Kvyat |
Red Bull | 0.996 | 19 |
| 8 | Nico Hulkenberg |
Force India | 1.016 | 15 |
| 9 | Valtteri Bottas |
Williams | 1.195 | 15 |
| 10 |  Felipe Massa |
Williams | 1.463 | 15 |
| 11 |  Carlos Sainz Jr. |
Toro Rosso | 1.568 | 20 |
| 12 |  Pastor Maldonado |
Lotus | 1.601 | 17 |
| 13 |  Max Verstappen |
Toro Rosso | 1.615 | 21 |
| 14 | Felipe Nasr |
Sauber | 1.706 | 17 |
| 15 |  Marcus Ericsson |
Sauber | 2.070 | 20 |
| 16 |  Romain Grosjean |
Lotus | 2.203 | 18 |
| 17 | Jenson Button |
McLaren | 2.997 | 12 |
| 18 | Will Stevens |
Marussia | 5.278 | 16 |
| 19 | Roberto Merhi |
Marussia | 5.297 | 9 |
| 20 | Fernando Alonso |
McLaren | no time | 1 |