The last 737-400 series flight touched down in Kuala Lumpur International Airport (KLIA) at 9.31pm Saturday, after taking off from the Bayan Lepas airport in Penang at 8.41pm.
It carried 85 passengers and was served by 10 cockpit and cabin crew.
Capt Wan Muzainal Wan Mahazir, 42, who piloted the aircraft, said he and his crew had fond memories of the 737-400.
"It has been a good, memorable 22-odd years that the 400 series has been servicing MAS.
"(We) still have vivid, fond memories from when we started our early days training on the 400 series, 20 years ago," he told reporters here.
He added that the 400 series would be replaced by the 737-800 series, of which there are 53 planes currently in service.
MAS chief executive Ahmad Jauhari Yahya said the 737-400 had an exemplary safety record.
"It's like the retiring of an old friend," he said, adding that MAS would be banking on the 800 series to ply the routes previously serviced by the 400 series.
Ahmad said the 800 series saves 15 per cent to 20 per cent more fuel compared to the 400 series, and could fly for five hours one-way.
Ahmad said MAS expected to see more deliveries of the 800 series this year and the next, with a total of 64 of the aircraft by year-end 2015.
MAS had eight of the 737-400 in service before they retired it.
The Boeing 737-400 entered MAS' service in May 1992, and at one point ran 54 of the aircraft, making the company the largest operator of the model outside the United States.