The two sides were doing battle for the fifth time this season, and just four days after a Premiership clash at the Reebok Stadium that had seen Wanderers run out 4-1 winners against an under-strength Hammers side.
This time around, and with a place in the last eight of the FA Cup at stake, Alan Pardew sent out his strongest 11, as Yossi Benayoun, Dean Ashton and Harewood all earned recalls, while captain Nigel Reo-Coker returned in midfield following illness.
Bolton boss Sam Allardyce made two changes to his line-up, as Ricardo Vaz Te made way for Abdoulaye Faye to add greater steel to the midfield, and Nicky Hunt replaced Joey O'Brien at right-back.
Just nine minutes in, it was Hunt who played a part in the opening goal, but unfortunately at the wrong end, as Harewood's low cross from the right fell to the England under-21 international, whose attempted clearance cannoned off his own goalkeeper Jussi Jaaskelainen and rolled into the empty net.
Having seen Bolton dominate first-half proceedings in the Premiership on Saturday, the Hammers were keen to take control on their own patch, and it was against the run of play that the visitors engineered an equaliser with their first effort on target just 14 minutes before the interval.
After Reo-Coker had lost possession in midfield, Kevin Nolan fed Kevin Davies, who was allowed time and space to turn on the edge of the penalty area before firing in a swerving shot that deceived Shaka Hislop and flew into the net.
Benayoun might have restored his team's advantage just before the break, when Reo-Coker played him in behind Ricardo Gardner, but the Israeli's effort was blocked by the legs of Jaaskelainen, and the two sides went in at the interval level.
The second half followed largely the same pattern as the first, with both sides generating a fair share of possession but the Hammers enjoying the better of the chances, with Harewood and Matty Etherington both going close midway through the half.
Indeed, Etherington looked to have made the breakthrough with just 20 minutes remaining, as he skipped past two defenders into the box, but Tal Ben Haim bravely threw himself in front of the winger's goalbound effort, to ensure that Bolton were still firmly in with a shout as the closing stages approached.
The visitors might have won it with just five minutes left, as a goalmouth scramble ended with the ball dropping at the feet of Davies, but the powerful striker could only hook his effort high over the bar, and the crowd of 24,685 were forced to endure another half an hour of nail-biting and sub-zero temperatures on a freezing cold evening in east London.
Just five minutes into extra-time, though, the claret and blue faithful were given every reason to feel warmed up, as Harewood grabbed what proved to be the winner.
Etherington was again involved in the build-up, jinking past two defenders before finding Benayoun on the right, whose inch-perfect near-post cross was met by an equally precise finish from Harewood, a clipped effort from six yards out giving Jaaskelainen no chance.
Even the shock sight of a smoke flare thrown from the crowd on to the pitch couldn't dampen the Hammers' celebrations, although the club may find themselves in hot water with the authorities for an incident that could have turned out to be much worse.
While Pardew may feel vindicated that his resting of several key players on Saturday, including Harewood, paid off in fitting style after 120 minutes of high-tempo football at Upton Park.