Included in the Boro side were returning loanees Matty Dolan, Ryan Brobbel and Connor Ripley, while the likes of Fabio, Jesse Lingard and Zaha were named in the United squad, the latter on the bench.
The home side started the game strongly and Will Keane saw two headed efforts go close. On 20 minutes Lingard, fresh from a spell on loan at Birmingham City, shot just wide from 20 yards.
Boro very nearly opened the scoring on 29 minutes. Jordan Jones played a beautiful through ball through to Cameron Park. Thorpe came in to clear but managed only to hit team-mate Ekangamene, and the ball went inches wide of the post with Johnstone stranded.
A minute later another Fabio cross found left back Blackett in space, but Ripley did excellently to smother his shot. Shortly afterwards Lingard tested Ripley's reflexes but found they were in full working order as he saved the wingers effort.
Despite the home side enjoying the lion share of possession, Boro were still creating chances. Thorpe had to intercept after an error from his defensive partner Ekangamene nearly let in Bradley Fewster. Park also saw a deflected shot go narrowly wide.
On the stroke of half-time Keane tried to lob Ripley but the saw the ball land on top of the net.
Half time: Manchester United U21s 0 Boro U21s 0
The Boro backline had England international Wilfried Zaha to contend with after he came on as an early second half substitute in place of Macheda.
On 58 minutes Fewster headed wide from a Jones corner and Ekangamene again nearly headed into his own net.
United thought they had opened the scoring when Keane volleyed in a pass from Petrucci but saw his effort ruled out due to offside.
Ripley continued to impress as he kept out a Keane header and then pulled off a remarkable one-handed save to deny Zaha.
Graeme Lee's men defended valiantly and there were great displays from all the back five. There was time for just one more chance when Thorpe again headed over.
Boro held onto to earn their first point away to Manchester United since a 1-1 draw in February 2007.
The point lifted Boro up to 18th place in the league table but only two points behind United, who sit in seventh position.
Full time: Manchester United U21s 0 Boro U21s 0
Manchester United: Johnstone; Fabio (Janko 71), Blackett (Pereira 81), Thorpe (Capt), Ekangamene, Cole, James, Petrucci, W Keane, Macheda (Zaha 55), Lingard. Unused subs: Gollini (GK), Rothwell
Middlesbrough: Ripley; B Halliday, Weledji, Burn, Bennett, Waters (Morris 64), Jones, Dolan (Capt), Fewster, Park (Kneeshaw 80), Brobbel (Kitching 80). Unused subs: Meling, Coddington (GK)
Referee: Simeon Lucas
Boro Man of the Match: Great defensive displays from Jonny Burn and Kieran Weledji in the heart of the Boro defence. However Connor Ripley, playing his first U21 game of the season, was immense. The save to deny Zaha especially worthy of note.