Before the kick-off, McClaren said: "With home games against Fulham and West Brom and a UEFA Cup tie in Holland in midweek, this is a very important stage of the season."
McLaren though, must have had some doubts as to whether his side would start off on the right note. For Boro it took a long time to get into their stride.
Fulham will have been disappointed with the result after twice taking the lead.
Middlesbrough were without Australian international goalkeeper Mark Schwarzer and striker Mark Viduka, who were both injured on World Cup duty against Uruguay.
Fellow Aussie Brad Jones took over in goal and was picking the ball out of the net before he even had time to get into the game.
It was a superb goal by Collins John. Tomasz Radzinski provided the pass for John to chest the ball down and fire the ball into the roof of the net from an acute angle.
It was an excellent piece of opportunism on the part of the youngster and a shock for Middlesbrough.
Boro, who had destroyed Manchester United in their previous home game, were struggling to hit form though Jimmy Floyd Hasselbaink should have done better from a cross field pass by Yakubu.
Hasselbaink completely missed his shot.
Brian McBride was not far off target for Fulham who showed good movement in the early stages.
Middlesbrough, however, threatened to level the scores after 27 minutes from a Fabio Rochemback corner before Boro full-back Franck Queudrue got in a header from a few yards out that struck Tony Warner when the goalkeeper knew little about it.
Middlesbrough were missing the midfield guile of Gaza Mendieta, with Fulham packing their defence to good effect.
There was a quiet atmosphere despite a near 28,000 crowd, fortunately, proceedings livened up after the break.
Boro brought on substitute Szilard Nemeth and switched to a 4-4-2 formation.
They piled on pressure in a bid for an early goal and Hasselbaink had the misfortune to strike team-mate Chris Riggott on the goal-line.
Middlesbrough drew level when James Morrison had the satisfaction of scoring his first Premiership goal.
Yakubu found Morrison at the far post with a left-wing cross and the youngster took full advantage.
Any hopes Middlesbrough had of then taking the lead were shattered when Fulham hit back with a goal from Papa Bouba Diop.
John sent over a right-wing corner and, with perfect timing, Diop climbed over the Boro defence to leave Jones helpless with a powerful header into the roof of the net.
The game was wide open at this stage. Middlesbrough were piling on pressure, but there was always the threat of a sharp counter attack from the London side.
Hasselbaink had a glaring miss when he shot into the sidenetting from four yards, but Yakubu followed up shortly after with his eighth goal of the season.
Skipper Gareth Southgate hit a left-wing cross across the face of the goal to the far post where Hasselbaink's effort hit Yakubu and went in from close range.
Fulham players protested vigorously with several going across to a linesman to complain, but referee Uriah Rennie waved aside their seemingly justified appeals for offside.
Hasselbaink then gave Boro a perfect boost for their midweek European adventure by cutting inside and hammering the winning goal six minutes from time.