The 23-time Isle of Man TT winner claimed back-to-back class wins in 2018 and 2019 after missing the race through injury in 2017.
McGuinness, who surpassed 100 TT starts in June, also won the race in 2016 and holds the lap record at 113.342mph.
The 50-year-old completed three laps in Sunday’s opening practice session and topped the times with a speed of 109.637 mph.
Practices were canceled on Monday due to wet weather and low cloud over the Isle of Man, but will resume on Tuesday evening, with roads closed from 6pm and the first bikes at 6.20pm.
McGuinness said: “I feel really good, happy and looking forward to riding the Paton again.
“It’s the same track and you have to respect the place. There is a little less pressure, but I still feel pressure here.
“I’m in the ballpark and it’s a fun bike to ride. You can put it anywhere you want compared to a Superbike, which tends to drive you.
“It’s quite difficult because you have to stay tucked in as much as possible and I don’t get any younger, and the belly doesn’t shrink,” he added.
“Everything has to be perfect and it’s almost like riding a 250, every gear change has to be perfect and you have to be really focused.
“I have to say I was quite jealous to see the guys go off on their Superbikes – maybe I should buy one for next year.”
Following Monday’s cancellation, an additional qualifying session is now scheduled for Wednesday afternoon, with roads closed from 12:30 p.m. to 4:30 p.m. The evening session will then also continue as planned (roads closed from 6 p.m. until 9 p.m. at the latest).
McCormack was a late replacement for Derek Sheils, who was unable to race the Manx GP due to family commitments.
James Hind (114.137mph) led Ballymoney man Michael Dunlop (112.611mph) in the lightweight 250cc class.
Dunlop completed a single lap in Crossan Motorcycles’ red and yellow livery – the same colors used by his legendary late father Robert when Michael began his racing career.
Stephen Smith led the MGP Senior race timesheets at 118.871 mph with Chris Moore fastest in the MGP Junior class at 112.778 mph.
The five-race schedule begins Friday with the Dunlop Lightweight race at 2:40 p.m.
On Saturday, the Classic Senior MGP is scheduled at 12:45 p.m. with the Junior MGP at 3:15 p.m.
The festival is set to end on bank holiday Monday with the Senior Manx Grand Prix (11:30 a.m.) and Classic Superbike race (2:15 p.m.). All races will be held over four laps.