Masakadza was spent earlier when he was dropped seven by Ariful Haque at the outset to join the debutant bowling and Khaled Ahmed.
Brian Chari, 10 was not out, and Donald Tiripano (naught) prevented further harm.
Zimbabwe, who is in the 1-0 competition in the two-game competition, needs to draw at least to win their first Test series in seven years.
But Mushfiqur sounded, removing Brendon Mavuta alone for one leg in a square after the tea break to become the first bat ever to score two double tons at Cricket Test.
"I was not in poor form in Tests, but I did not get a big insight. I think it's around the corner," said Mushfiqur at the end of playing a second day.
"I knew that a 50-minute conversion would make a big score. I had a lot of self-belief. I got my clips in place."
Mushfiqur, who played 421 kits and reaches 18 four and six, also surpassed Shakib to Hasan to become the top scorer in a session for Bangladesh at Test Cricket.
Skipper Mahmudullah called the bat's coat to the costume room shortly after Mushfiqur surprised Sean Williams for one to pass 217 Shakib against New Zealand in Wellington in 2017.
Mushfiqur shared a 144-run record with an untouched octave empty with Mehidy Hasan, after Kyle Jarvis took two breaks during the afternoon session to complete his third past five in Testing.
Mushfiqur also had a hand in the eighth previous wicket record when 113 added Naeem Islam against England in 2010.
Jarvis, who claimed to have three wickets on the opening day, removed Mahmudullah for 36 and Ariful Haque for four but Mushfiqur and Mehidy refused the visitors a further success.
Resume at 303-5, Bangladesh began to take care on day two, scoring just 22 runs in the first hour before Mushfiqur and Mahmudullah finally opened.
Mushfiqur, who is now six centuries old, has taken 56 balls to score his first border in the morning.
Zimbabwe suffered a blow when Tendai Chatara took her forward without a bust while damaging a ball in the morning.
Zimbabwe Cricket said Chatara had suffered a suspected quad muscle strain and was outside the game.
Zimbabwe won the opening by 151 running in Sylhet, their first Test award in five years