The 21-year-old rookie, in a Sauber car, lost control of his machine as he came out of the tunnel - at the same place where German Nico Rosberg suffered a similar crash during morning practice.
His car appeared to hit bumps in the surface of the circuit, lift to the left and then steer right into the barriers before slewing in a half-turn into a barrier at the chicane.
Perez hit the barrier side-on and the session was stopped immediately with a medical team and an ambulance going to the scene to attend to the driver.
"It was with great relief the Sauber F1 Team received the news that Sergio Perez has no serious injuries after his heavy accident in the closing minutes of the final part of qualifying for the Monaco Grand Prix," said Sauber in a statement, adding he was taken to the Hospital Princess Grace in Monaco.
"The doctors said Perez had suffered concussion and a strained thigh injury, but no broken bones and, following a scan, they could find no further injuries."
But a later statement said he will not race and the racer was expected to be detained overnight for observation.
Team chief Peter Sauber explained: "Of course, we are very relieved that Sergio wasn't seriously injured. Up to the accident, he was doing very well in qualifying, and also better than expected, as he had outperformed all his direct competitors."
Sauber added that it was a pity he could not race, but stressed it was the correct decision.
Perez's absence from the grid means team-mate Japanese Kamui Kobayashi will be the only Sauber driver in the race.
The collision came with less than three minutes remaining in qualifying and ripped off the front right wheel of his car as the vehicle rammed into the barriers twice.
The barriers into which Perez finally came to a halt were the same barriers into which Austrian Karl Wenglinger collided in 1994 - leaving him in a coma for nearly three weeks - and also Britons Jenson Button and David Coulthard.
Nicknamed 'Checo', Perez, from Guadalajara, is in his first season in Formula One and has established a reputation as one of the most talented, confident, and likeable, young drivers in the paddock.
His father Antonio, accompanied by the Sauber team manager Beat Zehnder, swiftly followed to the circuit medical centre following the accident. Perez was described by the team as being lucid and answering questions.