Dunlop led throughout and won by 13.3 seconds from Peter Hickman for his second victory of the week, and his third in the blue riband event.
The triumph sees the 28-year-old move into fourth place in the all-time solo winners' list.
The race was run over four laps after initially being red-flagged for an incident involving Ian Hutchinson.
Sixteen-time winner Hutchinson was taken by helicopter to Noble's Hospital after sustaining a broken femur in a crash at the 27th Milestone.
Dunlop had equalled the late Mike Hailwood's tally of 14 wins by taking victory in the Supersport race earlier in the week.
An opening lap of 132.29mph saw the Northern Irishman enjoy a 4.2 second lead over Hickman by the end of lap one and he increased that by five seconds thanks to a second circuit of 132.90.
"Today we have made the impossible possible on a brand new bike," said the Bennetts Suzuki rider, who also won the showpiece finale in 2014 and 2016.
"It was hard work and I was trying to go as easy on the bike as I could. The bike never missed a beat and everyone remembers who won the Senior."
Hickman, who had been battling for the lead with Hutchinson when the initial race was halted, secured his fifth podium from five starts, having never previously finished in the top three prior to this week.
Kawasaki rider Dean Harrison was 10 seconds behind the Lincolnshire rider in third to replicate his result in the Superbike race on Sunday.'
James Hillier, Michael Rutter and Josh Brookes completed the top-six leaderboard.
Manxman Conor Cummins ended eighth but his Padgett's Honda team-mate Bruce Anstey retired at Bedstead Corner on the second lap while contending for a rostrum place.
Michael Dunlop clinched his 15th TT success by winning Friday's restarted Senior race on the Isle of Man.